Conditions: Cutaneous Lupus Erythematosus
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 47
Healthy volunteers: no

Brief summary:
The primary objective of this study is to evaluate the efficacy of filgotinib and lanraplenib (formerly GS-9876) in females with moderately-to-severely active cutaneous lupus erythematosus (CLE).

Detailed description:

Arms:
arm 1: Lanraplenib + filgotinib placebo for 48 weeks arm 2: Filgotinib + lanraplenib placebo for 48 weeks arm 3: Filgotinib placebo + lanraplenib placebo for 12 weeks arm 4: After Week 12 Visit, participants on placebo will be rerandomized 1:1 and receive lanraplenib + filgotinib placebo in a blinded fashion through Week 48. arm 5: After Week 12 Visit, participants on placebo will be rerandomized 1:1 and receive filgotinib + lanraplenib placebo in a blinded fashion through Week 48.

Interventions: intervention 1: Lanraplenib intervention 2: Filgotinib intervention 3: Lanraplenib placebo intervention 4: Filgotinib placebo
Intervention descriptions: intervention 1: 30 mg tablets administered orally once daily with or without food intervention 2: 200 mg tablets administered orally once daily with or without food intervention 3: Tablets administered orally once daily with or without food intervention 4: Tablets administered orally once daily with or without food

Protocol document:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 2, Randomized, Double-blind, Placebo-controlled Study to 
Assess the Safety and Efficacy of Filgotinib and GS-9876 in Female
Subjects with Moderately-to-Severely Active Cutaneous Lupus 
Erythematosus (CLE)
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
ClinicalTrials.gov 
Identifier:
134040
Not applicable
NCT03134222
Indication:
Cutaneous lupus erythematosus
Protocol ID:
GS-US-436-4092
Gilead Clinical 
Program Manager:
Name:
Telephone:
Fax:
Gilead Medical 
Monitor:
Name:
Telephone:
Fax:
Mobile:
Protocol Version/Date:
Original:
19 December 2016
Amendment 1:
23 February 2017
Amendment 2:
30 June 2017
Administrative Amendment 3:
4 January 2018
Amendment 4:
15 October 2018
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or under 
control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, potential 
investigator, or consultant, for review by you, your staff, and an applicable Institutional Review Board or 
Independent Ethics Committee. The information is only to be used by you in connection with authorized 
clinical studies of the investigational drug described in the protocol. You will not disclose any of the 
information to others without written authorization from Gilead Sciences, Inc., except to the extent 
necessary to obtain informed consent from those persons to whom the drug may be administered.
PPD
PPD
PPD
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PPD
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(rJ GILEAiJ 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................5
LIST OF IN-TEXT FIGURES ......................................................................................................................................5
PROTOCOL SYNOPSIS ..............................................................................................................................................6
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................14
1.
INTRODUCTION ..............................................................................................................................................18
1.1.
Background ............................................................................................................................................18
1.2.
Filgotinib................................................................................................................................................19
1.2.1.
General Information .............................................................................................................19
1.2.2.
Nonclinical Pharmacology and Toxicology .........................................................................19
1.2.3.
Clinical Trials of Filgotinib..................................................................................................19
1.3.
GS-9876 .................................................................................................................................................19
1.3.1.
General Information .............................................................................................................19
1.3.2.
Nonclinical Pharmacology and Toxicology .........................................................................20
1.3.3.
Clinical Trials of GS-9876 ...................................................................................................22
1.4.
Rationale for This Study ........................................................................................................................23
1.4.1.
Rationale for Endpoint and Timing......................................................................................24
1.4.2.
Rationale for Dose................................................................................................................24
1.5.
Risk/Benefit Assessment for the Study..................................................................................................25
1.6.
Compliance ............................................................................................................................................26
2.
OBJECTIVES.....................................................................................................................................................27
3.
STUDY DESIGN................................................................................................................................................28
3.1.
Endpoints ...............................................................................................................................................28
3.2.
Study Design..........................................................................................................................................29
3.3.
Study Treatments ...................................................................................................................................29
3.4.
Duration of Treatment............................................................................................................................30
3.5.
Subject Discontinuation Criteria ............................................................................................................30
3.5.1.
Study Drug Interruption Considerations...............................................................................30
3.5.2.
Study Drug Discontinuation Criteria....................................................................................31
3.6.
End of Study...........................................................................................................................................32
3.7.
Post Study Care......................................................................................................................................32
3.8.
Biomarker Testing..................................................................................................................................33
3.8.1.
Biomarker Samples to Address the Study Objectives ..........................................................33
4.
SUBJECT POPULATION..................................................................................................................................35
4.1.
Number of Subjects and Subject Selection ............................................................................................35
4.2.
Inclusion Criteria....................................................................................................................................35
4.3.
Exclusion Criteria...................................................................................................................................37
4.4.
Screen Failures.......................................................................................................................................39
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................40
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................40
5.1.1.
Procedures for Breaking Treatment Codes...........................................................................40
5.2.
Description of Filgotinib and PTM Filgotinib........................................................................................40
5.2.1.
Formulation of Filgotinib and PTM Filgotinib.....................................................................40
5.2.2.
Packaging and Labeling of Filgotinib and PTM Filgotinib..................................................41


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5.3.
Description of GS-9876 and PTM GS-9876 ..........................................................................................41
5.3.1.
Formulation of GS-9876 and PTM GS-9876 .......................................................................41
5.3.2.
Packaging and Labeling of GS-9876 and PTM GS-9876 ....................................................41
5.4.
Storage and Handling of Study Drugs....................................................................................................41
5.5.
Dosage and Administration of Study Drugs...........................................................................................42
5.6.
Prior and Concomitant Medications.......................................................................................................42
5.6.1.
Allowed Concomitant Medications......................................................................................42
5.6.2.
Prohibited Concomitant Medications...................................................................................44
5.7.
Vaccine Guidelines ................................................................................................................................46
5.8.
Accountability of Study Drugs...............................................................................................................46
5.8.1.
Study Drug Return or Disposal ............................................................................................46
6.
STUDY PROCEDURES ....................................................................................................................................47
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................47
6.2.
Pretreatment Assessments......................................................................................................................47
6.2.1.
Screening Visit .....................................................................................................................47
6.2.2.
Day 1 Assessments...............................................................................................................48
6.3.
Randomization .......................................................................................................................................50
6.4.
Week 2 through Week 24 (Study Dosing Period)..................................................................................50
6.5.
Week 30 through Week 48 (24-week Extension Period) .......................................................................52
6.6.
Follow-up Assessments..........................................................................................................................54
6.7.
Early Termination Assessments.............................................................................................................55
6.8.
Unscheduled Visit Assessments.............................................................................................................57
6.9.
Study Assessments.................................................................................................................................57
6.9.1.
Priority of Assessments........................................................................................................57
6.9.2.
Efficacy ................................................................................................................................57
6.9.3.
Safety....................................................................................................................................59
6.9.4.
Clinical Laboratory Evaluations...........................................................................................59
6.9.5.
Vital Signs............................................................................................................................60
6.9.6.
Physical Examination...........................................................................................................60
6.9.7.
Other Safety Assessments ....................................................................................................60
6.10.
Pharmacokinetics Assessments..............................................................................................................60
6.11.
Biomarker Assessments .........................................................................................................................61
6.12.
Photography ...........................................................................................................................................61
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................62
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................62
7.1.1.
Adverse Events.....................................................................................................................62
7.1.2.
Serious Adverse Events........................................................................................................62
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................63
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................63
7.2.2.
Assessment of Severity ........................................................................................................64
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................64
7.3.1.
Adverse Events.....................................................................................................................64
7.3.2.
Serious Adverse Events........................................................................................................65
7.4.
Gilead Reporting Requirements.............................................................................................................66
7.5.
Clinical Laboratory Abnormalities.........................................................................................................66
7.6.
Toxicity Management ............................................................................................................................66
7.6.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................67
7.6.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................67
7.6.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................67
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7.7.
Special Situations Reports......................................................................................................................68
7.7.1.
Definitions of Special Situations..........................................................................................68
7.7.2.
Instructions for Reporting Special Situations.......................................................................69
8.
STATISTICAL CONSIDERATIONS................................................................................................................71
8.1.
Analysis Objectives and Endpoints........................................................................................................71
8.1.1.
Analysis Objectives..............................................................................................................71
8.1.2.
Primary Endpoint .................................................................................................................71
8.1.3.
Secondary Endpoints............................................................................................................71
8.1.4.
Exploratory Endpoints..........................................................................................................72
8.2.
Analysis Conventions.............................................................................................................................72
8.2.1.
Analysis Sets ........................................................................................................................72
8.3.
Data Handling Conventions ...................................................................................................................73
8.4.
Demographic Data and Baseline Characteristics ...................................................................................73
8.5.
Efficacy Analysis ...................................................................................................................................74
8.5.1.
Primary Analysis..................................................................................................................74
8.5.2.
Secondary and Exploratory Analyses...................................................................................74
8.6.
Safety Analysis.......................................................................................................................................74
8.6.1.
Extent of Exposure...............................................................................................................74
8.6.2.
Adverse Events.....................................................................................................................74
8.6.3.
Laboratory Evaluations ........................................................................................................75
8.6.4.
Other Safety Evaluations......................................................................................................75
8.7.
Pharmacokinetic Analysis......................................................................................................................75
8.8.
Biomarker Analysis................................................................................................................................75
8.9.
Sample Size............................................................................................................................................76
8.10.
Data Monitoring Committee ..................................................................................................................76
8.11.
Analysis Schedule ..................................................................................................................................76
9.
RESPONSIBILITIES..........................................................................................................................................78
9.1.
Investigator Responsibilities ..................................................................................................................78
9.1.1.
Good Clinical Practice..........................................................................................................78
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................78
9.1.3.
Informed Consent.................................................................................................................78
9.1.4.
Confidentiality......................................................................................................................79
9.1.5.
Study Files and Retention of Records ..................................................................................79
9.1.6.
Case Report Forms...............................................................................................................80
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................81
9.1.8.
Inspections............................................................................................................................81
9.1.9.
Protocol Compliance............................................................................................................81
9.2.
Sponsor Responsibilities ........................................................................................................................82
9.2.1.
Protocol Modifications.........................................................................................................82
9.2.2.
Study Report and Publications .............................................................................................82
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................82
9.3.1.
Payment Reporting...............................................................................................................82
9.3.2.
Access to Information for Monitoring..................................................................................83
9.3.3.
Access to Information for Auditing or Inspections ..............................................................83
9.3.4.
Study Discontinuation..........................................................................................................83
10.
REFERENCES ...................................................................................................................................................84
11.
APPENDICES ....................................................................................................................................................86
Appendix 1.
Investigator Signature Page....................................................................................................87


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Appendix 2.
Study Procedures Table..........................................................................................................88
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................92
Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) v4.03....................................93
Appendix 5.
Pregnancy Precautions, Definitions of Females of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................94
Appendix 6.
Clinical Laboratory Assessment Table...................................................................................97
Appendix 7.
Physician’s Global Assessment of CLE Disease Activity......................................................98
Appendix 8.
Subject Global Assessment of CLE Disease Activity and Other Subject Reported 
Measures.................................................................................................................................99
LIST OF IN-TEXT TABLES
Table 1.
Margins for GS-9876 Based on Systemic Exposure Relative to the Observed 
Human Exposure at 30 mg once daily (AUC)........................................................................22
Table 2.
Prohibited Medications...........................................................................................................44
Table 3.
Grading of Adverse Event Severity........................................................................................64
LIST OF IN-TEXT FIGURES
Figure 1.
Study Schema.........................................................................................................................29


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Assess 
the Safety and Efficacy of Filgotinib and GS-9876 in Female Subjects with 
Moderately-to-Severely Active Cutaneous Lupus Erythematosus (CLE)
IND Number:
EudraCT 
Number:
Clinical 
Trials.gov 
Identifier:
134040
Not applicable
NCT03134222
Study Centers 
Planned:
Approximately 20 centers in the United States (US) and Canada
Objectives:
The primary objective of this study is as follows:

To evaluate the efficacy of filgotinib and GS-9876 in female subjects
with moderately-to-severely active cutaneous lupus erythematosus 
(CLE)
The secondary objective of this study is as follows: 

To evaluate the safety and tolerability of filgotinib and GS-9876 in 
moderately-to-severely active CLE
The exploratory objectives of this study are as follows:
 
 
 
 
 
 
 
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Study Design:
This is a Phase 2, randomized, double-blind, placebo-controlled study to 
evaluate the safety and efficacy of filgotinib and GS-9876 in female 
subjects with moderately-to-severely active CLE.
Eligible subjects will be randomized 2:2:1 in a blinded fashion to 1 of 
3 arms and receive daily oral doses of the following study drugs starting on 
Day 1 for 12 weeks: 
Arm
Study Drugs
Filgotinib 200 mg (n=20)
filgotinib 200 mg + PTM GS-9876 30 mg
GS-9876 30 mg (n=20)
GS-9876 30 mg + PTM filgotinib 200 mg
Placebo (n=10)
PTM filgotinib 200 mg + PTM GS-9876 30 mg
PTM = placebo to match
On Day 1, randomization will be stratified by two factors: (i) disease 
subtype (chronic cutaneous lupus erythematosus [CCLE] (eg, discoid lupus 
erythematosus [DLE]) vs subacute cutaneous lupus erythematosus [SCLE]) 
and (ii) concurrent background disease-modifying antirheumatic drug 
[DMARD] use vs no use. 
At Week 12, upon completion of all scheduled assessments, subjects on 
placebo will be re-randomized 1:1 to receive filgotinib 200 mg + PTM 
GS-9876 30 mg once daily or GS-9876 30 mg + PTM filgotinib 200 mg 
once daily for the remainder of the study in a blinded fashion. Dosing and 
assessments for all subjects will continue through Week 24.
Subjects who have not permanently discontinued study drug dosing during 
the first 24-week period may enter the subsequent 24-week extension
period where they will continue to receive their assigned dose of study 
drug, in a blinded fashion.
Screening 
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Substudies:
 
 
 
Number of 
Subjects 
Planned:
Approximately 50 female subjects
Target 
Population:
Adult female subjects with moderately-to-severely active CLE
Duration of 
Treatment:
A maximum of 48 weeks of study drug
Diagnosis and 
Main 
Eligibility 
Criteria:
Main Eligibility Criteria:

Female, ≥ 18  ≤ 75 years of age at the time of consent

Must have a diagnosis of CLE, per investigator evaluation, with the 
following:
Moderately-to-severely active CLE (Cutaneous Lupus Disease Area 
and Severity Index [CLASI] activity score ≥ 10) at screening and 
Day 1
Prior intolerance or inadequate response to at least one of the listed 
medications for the treatment of CLE (Sections 4.2 and 4.3):

Stable dose (defined as no change in prescription for at least 28 days 
prior to Day 1) of antimalarials and/or topical or oral corticosteroids is 
permitted during the study (see Section 5.6.1 for dose restrictions and 
other details). Subjects who are not planning to continue these 
medications during the study must have discontinued them at least 
28 days prior to Day 1

Must not have used prohibited medications per Section 5.6.2
Study 
Procedures/
Frequency:
Study visits for all subjects will occur at:

Screening: Within 28 days prior to Day 1 

Study Dosing Period: Day 1 and at Weeks 2, 4, 8, 12, 14, 16, 20, and 
24 or early termination (ET; if applicable)
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Subjects who have not permanently discontinued study drug dosing during 
the first 24-week period may be eligible to enter the 24-week extension 
period:

24-week Extension Period: Weeks 30, 36, 42, and 48 or ET 
(if applicable)

Follow-Up (FU) Visit: A FU visit will be conducted 4 weeks after the 
last dose of study drug. Subjects who discontinue study drug ≥4 weeks 
prior to their last visit will not be asked to return for a FU visit
Screening Assessments:
Subjects who provide written informed consent will be screened for 
eligibility, and undergo the following tests/procedures: complete medical 
history (including demographics, surgical history, and CLE history with 
documentation of prior skin biopsy results, if available), review of 
medication use, complete physical examination, height, weight, Physician’s 
Global Assessment (PGA), CLASI, vital signs (blood pressure, heart rate, 
respiratory rate, and temperature), 12-lead electrocardiogram (ECG), 
clinical labs (chemistry, hematology, coagulation, urinalysis, and urine 
protein to creatinine ratio), hepatitis B virus (HBV) test, hepatitis C virus 
(HCV) test, human immunodeficiency virus type 1 and type 2 (HIV-1, 
HIV-2) test, QuantiFERON® TB Gold in Tube test (if applicable) and chest 
x-ray (if not obtained within 3 months prior to screening), C-reactive 
protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin A1c 
(HbA1c), thyroid stimulating hormone (TSH) test, urine drug and alcohol 
screen, serum pregnancy test (females of child-bearing potential only, as 
defined per protocol), follicle stimulating hormone (FSH) test (females of 
non-childbearing potential only, as defined per protocol),), and adverse 
event (AE) collection.
Day 1 through Week 24 (Study Dosing Period) Assessments:
Eligible subjects will be randomized on Day 1. Subjects will return to the 
study center at Weeks 2, 4, 8, 12, 14, 16, 20, and 24 and undergo the 
following tests/procedures: medical history updates (Day 1 only), review of 
medication use, symptom-driven physical examinations, PGA, CLASI, 
Subject’s Global Assessment and other subject-reported measures 
(visual analogue scales [VAS], 36-item Short Form Health Survey [SF-36], 
Dermatology Quality of Life Index [DLQI], and Treatment Satisfaction 
Questionnaire for Medication [TSQM]), weight, vital signs, 12-lead ECG 
(Week 24 only), clinical labs (chemistry, hematology, coagulation, 
urinalysis, and urine protein to creatinine ratio), HCV monitoring 
(Weeks 12 and 24; if applicable), CRP, ESR, fasting lipids (Day 1 and 
Weeks 12 and 24), urine pregnancy test (females of child-bearing potential 
only), quantitative serum immunoglobulin test (Day 1 and Weeks 8 and 
20), autoantibody panel and complement levels (Day 1 and Weeks 12 and 
24), detailed target lesion assessment, representative photographs of areas 


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with skin involvement (identifying subject features should be obscured, as 
much as possible), detailed mucous membrane assessment (Day 1 and 
Weeks 2, 12, 14, and 24), and AE collection.
At Week 12, upon completion of all scheduled assessments, subjects on 
placebo will be re-randomized 1:1 in a blinded fashion to receive 
filgotinib 200 mg + PTM GS-9876 30 mg once daily or 
GS-9876 30 mg + PTM filgotinib 200 mg once daily for the remainder of 
the study.
Subjects who discontinue study drug dosing at any time may continue with 
study visits, procedures, and assessments, if deemed medically appropriate 
by the investigator, but will not be eligible for entering the 24-week 
extension period. 
Weeks 30 through 48 (24-week Extension Period) Assessments:
Subjects who have not permanently discontinued study drug dosing in the 
first 24-week period may enter the subsequent 24-week extension period 
where they will continue to receive their assigned dose of study drug, in a 
blinded fashion. Subjects will return to the study center at Weeks 30, 36, 
42, and 48, and undergo the following tests/procedures: review of 
medication use, symptom-driven physical examinations, PGA, CLASI, 
Subject’s Global Assessment and other subject-reported measures, weight, 
vital signs, 12-lead ECG (Weeks 36 and 48), clinical labs (chemistry, 
hematology, coagulation, urinalysis, and urine protein to creatinine ratio), 
HCV monitoring (Weeks 36 and 48; if applicable), CRP, ESR, fasting 
lipids (Week 42 only), urine pregnancy test (females of child-bearing 
potential only), quantitative serum immunoglobulin test (Week 42 only), 
autoantibody panel and complement levels (Week 42 only), detailed target 
lesion assessment, representative photographs of areas with skin 
involvement (identifying subject features should be obscured, as much as 
possible), detailed mucous membrane assessment (Weeks 36 and 48), and 
AE collection.
Early Termination Visit Assessments:
Subjects who discontinue the study prematurely (prior to Week 24 or prior 
to Week 48 for subjects entering the 24-week extension period), will return 
to the study center for the early termination (ET) visit and undergo the 
following test/procedures: review of medication use, symptom-driven 
physical examination, PGA, CLASI, Subject’s Global Assessment and 
other subject-reported measures, weight, vital signs, 12-lead ECG (if not 
completed within the prior 12 weeks), clinical labs (chemistry, hematology, 
coagulation, urinalysis, and urine protein to creatinine ratio), HCV 
monitoring (if applicable, if not completed within the prior 12 weeks), 
CRP, ESR, urine pregnancy test (females of child-bearing potential only), 
complement levels, detailed target lesion assessment, representative 
photographs of areas with skin involvement (identifying subject features 
should be obscured, as much as possible), and AE collection. 


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Follow-up Visit Assessments: 
Subjects will return to the study center for a FU visit 4 weeks after their 
last dose of study drug. The follow-up visit will include: review of 
medication use, a symptom-driven physical examination, PGA, CLASI, 
Subject’s Global Assessment and other subject-reported measures (except 
for the TSQM), weight, vital signs, clinical labs (chemistry, hematology, 
coagulation, urinalysis, and urine protein to creatinine ratio), urine 
pregnancy test (females of childbearing potential only), complement levels, 
detailed target lesion assessments, representative photographs of areas with 
skin involvement (identifying subject features should be obscured, as much 
as possible), and AE collection. Subjects who discontinue study 
drug ≥4 weeks prior to their final study visit will not be asked to return for 
a FU visit.
Pharmacokinetic Assessments:
Blood samples for PK analysis will be collected at Week 2 (at least 
30 minutes and up to 3 hours postdose), anytime at Week 4, and within 
2 hours prior to study drug administration at Weeks 12 and 24.
Biomarker Assessments:
Blood samples will be collected at screening, predose on Day 1 and at 
Weeks 2, 4, 12, 24, 48 (for subjects who enter the 24-week extension 
period), FU, and ET visit (if applicable).  
Concomitant Medication Management:
Stable medications at Day 1 (per Section 5.6.1) are to be continued during 
the study. Refer to Section 5.6.2 for a list of prohibited medications.
Test Product, 
Dose, and Mode 
of 
Administration:
Filgotinib 200 mg tablet, oral, once daily
GS-9876 30 mg tablet, oral, once daily
Reference 
Therapy, Dose, 
and Mode of 
Administration:
Placebo to match filgotinib 200 mg tablet, oral, once daily
Placebo to match GS-9876 30 mg tablet, oral, once daily
Criteria for 
Evaluation:
Safety:
Safety will be assessed through AE reporting, clinical laboratory tests, vital 
sign assessments, physical examinations (complete and symptom-driven), 
and ECGs at various time points during the study.


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Efficacy:
The primary endpoint is:

Change in CLASI activity score from baseline to Week 12
The secondary endpoints are:

Proportion of subjects at Week 12 with decrease of ≥5 points in CLASI
activity score from baseline 

Proportion of subjects at Week 12 with no worsening in CLASI activity 
score from baseline (worsening defined as ≥3 point increase)

Proportion of subjects at Week 24 with decrease of ≥5 points in CLASI 
activity score from baseline 

Proportion of subjects at Week 24 with no worsening in CLASI activity 
score from baseline (worsening defined as ≥3 point increase)
Pharmacokinetics:
Plasma concentrations of filgotinib, its metabolite (GS-829845), and 
GS-9876 will be analyzed. 
Biomarkers:
Blood samples for assessment of markers of inflammation, immune status, 
and janus kinase (JAK)-signal transduction and activation of transcription 
(STAT) and spleen tyrosine kinase (SYK) pathway activation may be 
analyzed.  
Histopathologic, immunohistochemistry (IHC), and gene expression 
assessments may be performed on available biopsies.  
 
Statistical 
Methods:
The primary analysis set for efficacy analyses will be the Full Analysis Set 
(FAS), which includes all randomized subjects who received at least one 
dose of study drug.
The primary endpoint is the change in CLASI activity score from baseline 
to Week 12. The primary analysis will consist of superiority test of 
filgotinib 200 mg versus placebo and GS-9876 30 mg versus placebo, 
respectively.
All continuous endpoints will be summarized using an 8-number summary 
(n, mean, standard deviation [SD], median, 1st quartile [Q1], 3rd quartile 
[Q3], minimum, maximum) by treatment arm and by study part. All 
categorical endpoints will be summarized by the number and percentage of 
subjects who meet the endpoint definition.
Safety endpoints will be analyzed by the number and percent of subjects 
with events or abnormalities for categorical values or 8-number summary 
(n, mean, SD, median, Q1, Q3, minimum, maximum) for continuous data 
by treatment arm.
CCI


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The primary analysis will be conducted when all enrolled subjects either 
complete their Week 12 visit or prematurely discontinue from the study.
The final analysis will be performed when all subjects complete the study 
or prematurely discontinue from the study. 
Sample Size:
With a sample size of 50 subjects (20 in each active treatment arm and 
10 in the placebo arm), there is a 79% power to detect a 2-point difference 
between each active arm and the placebo arm in the primary endpoint using 
a 2-sided 0.1-level test, assuming a common standard deviation of 2 and a 
10% drop-out rate per arm.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
ACLE
acute cutaneous lupus
ACR20
American College of Rheumatology 20% improvement
AE
adverse event
AhR
aryl hydrocarbon receptor
ALT
alanine aminotransferase
ANA
antinuclear antibody
ANC
absolute neutrophil count
APLA
antiphospholipid antibody
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
ATP
adenosine triphosphate
AUC
area under the curve
AUROC
area under the receiver operating characteristic curve
BAP
biomarker analysis plan
BCR
B-cell receptor
BCRP
breast cancer resistance protein
bDMARD
biologic disease-modifying antirheumatic drugs
BLQ
below the limit of quantitation
CCLE
chronic cutaneous lupus erythematosus
CD
cluster determinant
CD
Crohn’s disease
CES
carboxylesterases
CIA
collagen-induced arthritis
CK
creatinine kinase
CLASI
Cutaneous Lupus Erythematosus Disease Area and Severity Index
CLcr
creatinine clearance
CLE
cutaneous lupus erythematosus
Cmax
maximum observed plasma concentration
CNS
central nervous system
CRO 
contract research organization
CRP
C-reactive protein
csDMARD
conventional synthetic disease-modifying antirheumatic drug
CTCAE
Common Terminology Criteria for Adverse Events
CYP
cytochrome P450 enzyme
DLE
discoid lupus erythematosus
DLQI
Dermatology Life Quality Index
DMARD
disease-modifying antirheumatic drug
DMC
data monitoring committee 


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DNA
deoxyribonucleic acid
dsDNA
double stranded DNA
DSPH
(Gilead) Drug Safety and Public Health
EC50
half-maximal effective concentration 
ECG
electrocardiogram
eCRF
electronic case report form
ENA
extractable nuclear antigen
eSAE
electronic serious adverse event form
ESR
erythrocyte sedimentation rate
ET
early termination
EU
European Union
FAS
full analysis set
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
FU
follow-up
GCP
good clinical practice
GI
gastrointestinal
Gilead
Gilead Sciences, Inc.
GLP
Galapagos
HBsAg
hepatitis B surface antigen  
HBV
hepatitis B virus
HCV
hepatitis C virus
HDL
high-density lipoprotein 
HDPE
high density polyethylene 
hERG
human ether-a-gogo related gene
HIV
human immunodeficiency virus
HR
heart rate
IB
investigator’s brochure
IC50
half maximal inhibitory concentration
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
independent ethics committee
IFN
Interferon 
Ig
immunoglobulin
IHC
immunohistochemistry
IMP
investigational medicinal product
INR
international normalized ratio
IRB
Independent Review Board
IUD
intrauterine device
IWRS
interactive web response system


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JAK
janus kinase
LDL
low-density lipoprotein
LLOQ
lower limit of quantitation
MCV
mean corpuscular volume
MMRM
mixed model for repeated measures 
MTX
Methotrexate 
NOAEL
no observed adverse effect level
NOELs
no observed effect levels
NSAID
nonsteroidal anti-inflammatory drug
OATs
organic anion transporters
P protein
phosphorylated protein
PBMC
peripheral blood mononuclear cells
PD
pharmacodynamics
PGA
Physician’s Global Assessment
P-gp
P-glycoprotein
PK
pharmacokinetics
PT
preferred term
PT
prothrombin time 
PTM
placebo to match
PXR
pregnane X receptor
Q1
first quartile
Q3
third quartile
QT
electrocardiographic interval between the beginning of the Q wave and termination of the 
T wave, representing the time for both ventricular depolarization and repolarization to 
occur
QTc
QT interval corrected for heart rate 
QTcF
QT interval corrected for heart rate using the Fridericia formula
RA
rheumatoid arthritis
RBC
red blood cell 
RNA
ribonucleic acid
SADR
serious adverse drug reaction
SAE
serious adverse event
SAP
statistical analysis plan 
SCLE
subacute cutaneous lupus erythematosus
SD
standard deviation
SF-36
36 Item Short Form Health Survey
SLE
Systemic lupus erythematosus
SLEDAI-2K
systemic lupus erythematosus disease activity index 2000
SOC
system organ class
SjS
Sjogren’s syndrome


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Sm
Smith antigen
SSA
Sjogren’s-syndrome-related antigen A
SSB
Sjogren’s-syndrome-related antigen B
STAT
signal transduction and activation of transcription
SUSAR
suspected unexpected serious adverse reaction
SYK
spleen tyrosine kinase
TB
tuberculosis
TEAEs
treatment emergent adverse events
TLR
Toll-like receptor 
TNFα
tumor necrosis factor alpha
TSH
thyroid-stimulating hormone
TSQM
Treatment Satisfaction Questionnaire for Medication
TYKs
tyrosine kinases
UGT
uridine disphosphate glucuronosyltransferase
ULN
upper limit of normal
US
United States
VAS
visual analogue scale
vfPBMCs
viably frozen peripheral blood mononuclear cells
VL
viral load
WBC
white blood cell


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1.
INTRODUCTION
1.1.
Background
Cutaneous lupus erythematosus (CLE) is a chronic autoimmune disorder, most commonly 
diagnosed in women 20-50 years of age. Approximately 1/3 of women who are diagnosed with 
CLE also develop systemic lupus erythematosus (SLE) {Wieczorek 2014}. In a study of over 
1,000 patients with CLE in Sweden, it was found that 24% of the patients carried a diagnosis of 
SLE, while another 18% gained a diagnosis of SLE over a 2 year period {Gronhagen 2011}. 
Thus, treatment and monitoring of CLE includes ongoing assessment for and/or treatment of 
SLE, which is also highly female-predominant.
Cutaneous lupus is histologically characterized by interface dermatitis, in which lymphocytes 
infiltrate the basal epidermis and induce apoptosis of keratinocytes, resulting in hydropic 
degeneration with colloid bodies. Inflammation in CLE is mediated in part by type I interferons 
as well as Toll-like receptor (TLR)-dependent and -independent mechanisms. Subtypes of CLE 
include: chronic cutaneous lupus erythematosus (CCLE), subacute cutaneous lupus
erythematosus (SCLE), and acute cutaneous lupus erythematosus (ACLE). The most common 
subtype of CLE is CCLE, and in particular discoid lupus erythematosus (DLE) which accounts 
for approximately half of all CLE {Jarrett 2016}.  A diagnosis of ACLE in isolation will not 
qualify a subject for entry into this study. 
Overall, therapeutic options for CLE are limited {Winkelmann 2013}. There are few approved 
disease-modifying antirheumatic drugs (DMARDs) for CLE, and very limited clinical trial data 
in CLE for the biologic and synthetic DMARDs that have been approved for other indications. 
Avoidance of sunlight and topical sunscreen often help to limit disease flares, due to the 
photosensitive nature of the disease. Topical preparations of corticosteroids (eg, clobetosol), or 
injectable corticosteroids are commonly used, as well as topical immunosuppressants 
(eg, tacrolimus). Antimalarials (eg, chloroquine or hydroxychloroquine) are among the most 
common oral medications used. Other drugs used for CLE include: methotrexate (MTX), 
azathioprine, biologic disease-modifying antirheumatic drugs (bDMARDs; such as rituximab or 
belimumab), cyclophosphamide, cyclosporine, dapsone, gold salts, intravenous immunoglobulin 
(IVIG), mycophenolate, retinoids, and thalidomide, but efficacy with these agents is variable and 
toxicities can be dose limiting.
Filgotinib (GS-6034, formerly GLPG0634) is a potent and selective oral inhibitor of janus kinase
(JAK) 1 being developed by Gilead Sciences, Inc. (Gilead) and Galapagos (GLP) NV. 
Janus kinase 1 is believed to play an integral part in the pathogenesis of various autoimmune 
diseases, due its role in inflammatory cytokine signaling.  
GS-9876 is a potent and selective oral inhibitor of spleen tyrosine kinase (SYK) being developed 
by Gilead for the treatment of inflammatory diseases. Spleen tyrosine kinase is a cytoplasmic 
tyrosine kinase (TYK) primarily expressed in cells of the hematopoietic lineage, where it 
functions as a key signaling molecule mediating immunoreceptor signaling. Given its central role 
in immune cell signaling, inhibition of SYK is expected to affect multiple steps in the 
pathogenesis of several autoimmune diseases resulting in pleiotropic anti-inflammatory effects.


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1.2.
Filgotinib
1.2.1.
General Information
For further information on filgotinib, refer to the current investigator’s brochure (IB).
1.2.2.
Nonclinical Pharmacology and Toxicology
Filgotinib is a highly selective, adenosine triphosphate (ATP)-competitive inhibitor of JAK1. In 
cellular assays, it inhibits JAK/signal transduction and activator of transcription (STAT)-driven 
processes with half maximal inhibitory concentration (IC50) values from 179 nM upwards; in 
human whole blood assays, filgotinib exhibits approximately 30-fold selectivity over JAK2. 
Filgotinib demonstrated significant efficacy in the rat collagen-induced arthritis (CIA) model as 
well as in the mouse dextran sulphate sodium (DSS)-induced colitis model. Filgotinib’s 
metabolite, GS-829845, exhibits a similar JAK1 selectivity profile, but is approximately 
10 to 20-fold less potent than filgotinib.
In rats, filgotinib and GS-829845 had no effects on the respiratory system and CNS and no 
relevant effects on cardiovascular parameters (human ether-a-gogo related gene [hERG] and dog 
telemetry studies), apart from a slight non-adverse increase in heart rate and arterial pressure 
with GS-829845, at exposures 7-fold that of the Cmax in human subjects dosed with filgotinib 
200 mg once daily.
In repeat oral dose toxicity studies in both rats and dogs, the primary target tissues identified for 
filgotinib and GS-829845 were the lymphoid tissues which are expected based on the 
pharmacology of JAK inhibition. Additional filgotinib-related findings were observed in the 
testes of both species, and in the incisor teeth of rats. Effects on the lymphoid system were fully 
reversible. 
Filgotinib and GS-829845 are non-genotoxic.  
In embryofetal development studies, filgotinib and GS-829845 caused embryolethality and 
teratogenicity in rats and rabbits at exposures similar to the human exposure at 200 mg
once daily of filgotinib in subjects with RA. Administration of filgotinib did not affect female 
fertility, however, impaired male fertility was observed in rats at exposures approximately 15-
fold the human exposure at 200 mg of filgotinib in subjects with RA. The metabolite, GS-
829845, did not have any effects on fertility parameters.
1.2.3.
Clinical Trials of Filgotinib
A detailed description of all clinical studies can be found in the filgotinib IB.
1.3.
GS-9876
1.3.1.
General Information
For further information on GS-9876, refer to the current IB.


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1.3.2.
Nonclinical Pharmacology and Toxicology
1.3.2.1.
Nonclinical Pharmacology and Safety Pharmacology
GS-9876 is a selective and potent ATP-competitive inhibitor of SYK with an IC50 value of 
9.5 nM. Overall, GS-9876 is at least 7-fold more selective biochemically for SYK relative to all 
other protein kinases assayed. Functionally, GS-9876 inhibited anti-immunoglobulin (Ig) 
M-induced B-cell receptor (BCR)/SYK-mediated phosphorylation and activation of multiple 
downstream signaling pathways in primary human B-cells, suppressed anti-IgM mediated cluster 
determinant (CD) 69 and CD86 activation marker expression on B-cells, and proliferation of 
peripheral B cells. GS-9876 inhibited immune-complex stimulated tumor necrosis factor alpha 
(TNFand IL-1release from primary human monocytes. In human blood, GS-9876 inhibited 
SYK autophosphorylation, anti-IgD/BCR-induced CD69 expression on B-cells, and 
anti-FceRI-stimulated CD63 expression on basophils with geometric mean half-maximal 
effective concentration (EC50) values ranging from 171 nM to 301 nM.
In a MRL/lpr murine model of lupus, SYK inhibition showed a dose-responsive decrease in 
anti-dsDNA antibody titers and inhibition of proteinurea with an estimated SYK trough target 
inhibition of 50%. FACS analysis of splenic lymphocyte populations at study termination 
showed significant changes in lymphocyte subsets and activation markers with SYK inhibition 
including significant reductions in the percentage of follicular (CD19+/CD21+/CD23+) and 
mature (CD19+/IgM-/IgD+) B cells, as well as activated plasma cells (CD19+/CD138+/CD69+). 
Activated Thelper cells (CD4+CD69+) and central memory T cells (CD4+/ CD44+/CD62L+) were 
also reduced. A trend toward improved renal histopathology was observed with SYK inhibition.
In two independent rat CIA models in animals with established disease, GS-9876 caused 
significant and dose-dependent amelioration of clinical disease and histopathologic signs.
Histological evaluation of joints demonstrated that GS-9876 reduced pannus formation, cartilage 
damage, bone resorption, and periosteal bone formation. Significant efficacy was seen with 
GS-9876 doses that produced Cave exposures that were calculated to inhibit SYK phosphorylation 
by EC50. GS-9876 was well tolerated at all doses and there were no treatment-related adverse 
effects on body weight, food and drink intake, in-life observations or clinical pathology 
parameters.  
Safety pharmacology studies showed no clinically-relevant effects on the respiratory, and CNS 
systems after single oral doses up to 300 mg/kg. Cardiovascular effects in telemetered 
cynomolgus monkeys at ≥20 mg/kg included prolonged QTc interval from 5 through 25 hours 
postdose, slightly higher systolic, diastolic, and mean arterial pressure with lower heart rate 
through 6 hours postdose, and higher heart rate from 9 through 25 hours postdose. While 
differences in QTc interval were generally small, the changes were of sufficient magnitude to be 
considered biologically relevant. There were no inhibitory effects on the hERG potassium 
current when GS-9876 was tested up to a free drug concentration of 30 μM, which is
approximately 207-fold above the observed steady state Cmax at a 30 mg once daily dose. Further, 
no cardiovascular effects were observed in telemetered cynomolgus monkeys administered 
GS-9876 for 39 weeks at doses up to 15 mg/kg/day. The potential for GS-9876 to prolong the 
QTc interval was assessed with intensive time-matched electrocardiogram (ECG) monitoring in 
Gilead clinical studies GS-US-379-1372 and GS-US-379-1900, and no clinically significant 
changes in time-matched QTc intervals or in serial vital sign measurements were observed.


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1.3.2.2.
Nonclinical Toxicology
In repeat-dose studies, toxicity was assessed in rats and monkeys administered GS-9876 orally 
for up to 39 weeks. Dose-dependent effects on lymphocytes in both rats and monkeys were 
consistent with the expected pharmacology of SYK inhibition. Effects observed in rats and 
monkeys were increased erythrocyte turnover in rats at ≥10 mg/kg/day, and hemorrhage and 
thrombosis in monkeys at ≥20 mg/kg/day. At higher doses in rats (≥30 mg/kg/day), mortality 
associated with bacterial infections was seen, likely resulting from the immunomodulatory 
activity of GS-9876. Additional findings included lymphoid depletion in the thymus, changes in 
the pancreas, with secondary effects related to the immunomodulatory activity of GS-9876, and
opportunistic bacterial infection, observed in several tissues. The no-observed-adverse-effect 
level (NOAEL) in rats was 10 mg/kg/day after 26 weeks dosing. For the highest proposed
clinical dose of 30 mg once daily, estimated exposure margins are 2.4-/5.9- fold based on 
exposures at the NOAELs in the 26 week study in male/female rats, respectively.  
In the 28-day monkey study, there were no adverse effects at doses up to 10 mg/kg/day, with
hemorrhagic/thrombotic effects noted at 20 mg/kg/day. In the 39-week monkey study, there was 
no evidence of effects on hemostasis, and the NOAEL was 15 mg/kg/day, associated with an 
AUC0-24hr of 8040 ng•h/mL. One animal administered 15 mg/kg/day was sacrificed for humane 
reasons with persistent fecal changes, weight loss, deteriorating clinical condition, and large 
bowel inflammation. The moribund condition of this animal was not considered directly related 
to GS-9876 administration.  For the 30 mg dose in planned Study GS US-436-4092, the 
estimated exposure margins is 2.2-fold based on exposures at the NOAEL in the 39-week study 
in monkeys , and 1.2-fold based on exposures at the mid dose of 10 mg/kg/day. In clinical 
studies GS-US-379-1372 and GS US-379-1900 no changes in platelets numbers, prothrombin 
time (PT), partial thromboplastin time (PTT), international normalized ration (INR) or bleeding 
time were observed. 
In the pivotal developmental toxicity studies in pregnant rats and rabbits, there were no fetal 
malformations. At doses associated with significant maternal toxicity (reduced body weight gain 
and food consumption in rats and rabbits, and mortality and one abortion in rabbits), increases in 
post-implantation loss and late resorptions, reduced fetal body weights and fetal variations 
(delayed ossification) were noted in rats, with reduced fetal body weights in rabbits. In rats, the 
maternal NOAEL and embryo-fetal development NOEL was 30 mg/kg/day. In rabbits, the 
maternal NOAEL was not determined < 10 mg/kg/day and the embryo-fetal development NOEL 
was 10 mg/kg/day. For the 30 mg dose in planned Study GS-US-436-4092, estimated exposure 
margins are 23- and 1.0-fold compared to exposures at the fetal NOELs in rats and rabbits, 
respectively.GS-9876 was negative in the bacterial reverse mutation (Ames) assay, in vitro 
chromosomal aberration assay, and in vivo rat micronucleus assay and is therefore considered to 
be nongenotoxic. In the in vitro chromosome aberration assay in human lymphocytes, slight, but 
statistically significant increases in the number of polyploid cells was observed at the highest 
GS-9876 dose level evaluated. GS-9876 did not induce structural chromosome breakage when 
evaluated in the in vitro assay. 


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Table 1.
Margins for GS-9876 Based on Systemic Exposure Relative to the 
Observed Human Exposure at 30 mg once daily (AUC)
Species
Duration
Route
NOAEL
(mg/kg/day)
AUC0-24
(ng•h/mL)a
Marginb
Rat
Once daily 
x 26 weeks
Oral
10
8,800/21,800
(male/female)
2.4/5.9
(male/female)
Cynomolgus Monkey
Once daily 
x 39 weeks
Oral
15
8,040
2.2
NOAEL = no observed adverse effect level. 
a
Week 26 male and female rat AUC and week 39 Cynomolgus monkey AUC (combined sex)
b
Margins of exposure were calculated using observed steady-state exposure (AUCtau) in humans of 3708 ng•h/mL at 30 mg 
once daily in study GS-US-379-1900
1.3.2.3.
Nonclinical Drug Metabolism and Pharmacokinetics
GS-9876 exhibits high absorption in rats, dogs and monkeys. Plasma protein binding is moderate 
in all species with the mean free fraction in humans of 20.4%.
After oral dosing to albino and pigmented rats, recovery of [14C]GS-9876-derived radioactivity 
was high (≥ 97.8%) and the main route of elimination of GS-9876 was hepatobiliary with 
≤5.1% orally dosed radioactivity found in urine and 69.4% in bile.
In vitro, GS-9876 exhibits high metabolic stability with human hepatocytes, liver fractions and 
individual metabolizing enzymes. GS-9876 had little inhibitory effect on the activities of the 
major human drug metabolizing CYP enzymes and was a weak inhibitor of human UGT1A1. 
GS-9876 is a weak inhibitor of P-glycoprotein (P-gp) and breast cancer resistance protein 
(BCRP) and is a substrate for those efflux transports. It is a weak inhibitor of the hepatic uptake 
transporters organic ion transporter (OAT) P1B1 and OATP1B3 but is a substrate for neither. 
Drug-drug interactions in vivo are unlikely through inhibition of human CYP enzymes, 
UGT1A1, or efflux or uptake transporters. The potential of GS-9876 to cause drug-drug 
interactions through induction is low as there is little activation of pregnane x receptor (PXR) or 
aryl hydrocarbon receptor (AhR) in vitro.
1.3.3.
Clinical Trials of GS-9876
A detailed description of all clinical studies with GS-9876 may be found in the most current IB.
Completed Clinical Trials
GS-US-379-1372: This was a first-in-human, Phase 1, single-dose ranging study of GS-9876 in 
healthy adult volunteers to evaluate the safety, tolerability, PK, pharmacodynamics (PD), food 
effect, and drug-drug interaction potential using omeprazole. No risks were identified and no 
grade 3 or 4 AEs were reported. There were no clinically significant changes in vital signs, 
physical findings, laboratory parameters, or ECGs.
GS-US-379-1900: This was a single- and multiple-dose Phase 1 study of GS-9876 in healthy 
volunteers to evaluate the safety, tolerability, PK and PD of GS-9876. No risks were identified, 
all AEs were Grade 1 in severity. No dose relationships were observed between GS-9876 and 


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any AE. No AE was assessed by the investigator as related to study drug .There were no 
clinically significant changes in vital signs, physical findings, laboratory parameters, or ECGs. 
GS-US-379-1582: This was a proof of concept trial in subjects with RA to evaluate efficacy, 
safety, tolerability and PK of GS-9876. GS-9876 was well-tolerated and no safety signals were 
identified.
Ongoing Clinical Trials
GS-US-379-1932: This is a Phase 1, open-label study in subjects with impaired renal function to 
evaluate the PK of GS-9876.
GS-US-445-4189: This is a Phase 2, randomized, double-blind, placebo-controlled study to 
assess the safety and efficacy of filgotinib, GS-9876, and GS-4059 in adult subjects with active 
Sjogren’s Syndrome.
GS-US-437-4093: This is a Phase 2, randomized, double-blind, study in subjects with lupus 
membranous nephropathy (LMN) to evaluate the safety and efficacy of GS-9876 and filgotinib.
1.4.
Rationale for This Study
Although CLE affects approximately 70 per 100,000 persons in the United States (US), 
therapeutic options for CLE are limited {Winkelmann 2013}. There are few approved DMARDs 
for CLE (eg, hydroxychloroquine and MTX), and very limited clinical trial data in CLE for the 
various newer biologic and synthetic DMARDs that have been approved for other indications. 
Some individuals with CLE have an inadequate response or intolerance to available therapies.
The most common oral therapy for CLE, hydroxychloroquine, has a rare, but serious cumulative 
risk of irreversible retinopathy which potentially limits its long-term use. There is an unmet need 
for orally administered therapies with novel and targeted mechanisms of action that can safely 
and effectively improve the disease.
Filgotinib is an orally administered, small molecule inhibitor of JAK1, an intracellular TYK
dysregulated in subjects with inflammatory disorders. Filgotinib has demonstrated clinical 
activity and a favorable safety and tolerability profile in Phase 2 studies in subjects with 
moderately to severely active RA. Janus kinase 1 activation is required for type I interferon 
(IFN) signaling, which is thought to be central to both systemic and cutaneous lupus. Further, in 
vivo studies using a JAK1/JAK2 inhibitor (ruxolitinib) attenuated the development of skin 
lesions in the MRL/lpr mouse model of lupus {Chan 2015}.
Given its central role in immune cell signaling, inhibition of SYK is expected to have pleiotropic 
anti-inflammatory effects and affect multiple steps in CLE pathogenesis. B cells have been 
implicated in the pathogenesis of CLE as demonstrated by an increased number of B cells in the 
peripheral blood and lesions of individuals with DLE {Wouters 2004}. B cell depletion 
demonstrates an effect in individuals with certain types of CLE {Vital 2015}. As a critical 
mediator of BCR signaling, SYK inhibition suppresses BCR-stimulated proliferation, 
co-stimulatory molecule expression, and autoantibody production {Braselmann 2006, Coffey 
2012}. Phosphorylated SYK and SYK-associated genes are highly expressed in several cell types 
in CLE skin including keratinocytes and infiltrating immune cells. Further, inhibiting SYK in 


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vitro decreases keratinocyte expression of pro-inflammatory cytokines {Braegelmann 2016}. 
Spleen tyrosine kinase inhibition in two lupus-prone mouse models (MRL/lpr and BAK/BAX) 
suppresses skin disease {Deng 2010}.
The data suggest that inhibition of SYK or of JAK1 may decrease several processes implicated 
in CLE pathophysiology including B-cell and T-cell activation. 
1.4.1.
Rationale for Endpoint and Timing
Change in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)
activity score will be the primary measure of efficacy compared to placebo. The CLASI is a 
standardized measure of cutaneous-lupus disease activity and damage widely used in clinical 
studies {Klein 2010}. Secondary measures will include physician and subject reported outcomes. 
Quality of life will be measured using validated questionnaires including the Dermatology 
Quality of Life Instrument (DLQI) {Holm 2016} and the 36 Item Short Form Health Survey 
(SF-36). Satisfaction with the study drugs will be measured using the Treatment Satisfaction 
Questionnaire for Medication (TSQM).
Given the chronic nature of CLE, the primary endpoint (change in the CLASI activity score) will 
be assessed at Week 12 to provide adequate time for clinical response in skin scores. The 
selection of this time point is based on prior studies of CLE and other dermatological 
inflammatory conditions such as plaque psoriasis {Schmitt 2014} and on the speed of action of 
filgotinib (approximately 80-90% of total clinical benefit achieved by week 12), as demonstrated 
in Phase 2b studies of subjects with active RA (protocols GLPG0634-CL-203 and 
GLPG0634-CL-204). Review of the published information on prior randomized studies in CLE 
demonstrates a range of drug administration duration between 8 weeks for hydroxychloroquine 
{Ruzicka 1992} and 6 months for MTX {Carneiro 1999}, supporting the idea that a 12 week 
primary endpoint is both clinically and ethically appropriate and allows an acceptable time to 
assess initial response to therapy.
1.4.2.
Rationale for Dose
Enrolled subjects will be randomized to receive once daily oral filgotinib (200 mg), GS-9876 
(30 mg), or matched placebo tablets. The regimens of filgotinib and GS-9876 are based on safety 
data from clinical studies and supported by non-clinical safety data. Clinical efficacy data further 
support the filgotinib dose.
Results from Phase 2a studies (GLPG-CL-201 and GLPG-CL-202) and Phase 2b studies 
(GLPG-CL-203 and GLPG-CL-204) showed that 200 mg once daily filgotinib was well tolerated 
and demonstrated clinical efficacy (ACR20/50/70 and DAS28[CRP]) in subjects with RA. 
Exposure-response analysis of data from Phase 2 studies indicated a dose-dependent increase in 
efficacy, with a plateau at the 200 mg total daily dose on the dose-response curve. These results 
are consistent with the relationship observed between filgotinib exposures and pSTAT1 
activation (ex-vivo) following single and multiple filgotinib doses, where maximal inhibition of 
pSTAT1 (~78%) was achieved at or above the 200 mg total daily dose {Namour 2015}. Safety 
data collected across Phase 2 clinical studies showed no dose-dependent trends in the incidence 


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of AEs or SAEs. Based on the overall risk-benefit observed in Phase 2b studies, as well as the 
clinical overlap of RA and CLE, 200 mg once daily filgotinib is expected to be a safe dose to 
evaluate efficacy in subjects with CLE.
A 30 mg once daily dose of GS-9876 will be investigated in this study. In the multiple ascending 
dose study (GS-US-379-1900), GS-9876 doses of up to 50 mg once daily for 7 days were well 
tolerated in healthy volunteers. A trial of GS-9876 30 mg once daily is also under investigation 
in subjects with RA (GS-US-379-1582). Based on the similarity in risk-benefit profiles between 
RA and CLE, a 30 mg once daily dose is expected to have an acceptable safety profile and have 
the potential to be efficacious in CLE.
The totality of available data support the use of filgotinib 200 mg once daily and GS-9876 30 mg 
once daily for Phase 2 evaluation.
1.5.
Risk/Benefit Assessment for the Study
Based on the clinical data to date, as well as the data from nonclinical efficacy and mechanistic 
studies, there is a positive benefit-risk ratio for the development of filgotinib and GS-9876 in this 
underserved disease. This is particularly true for patients with CLE, who are at an increased risk 
of developing or having concomitant systemic disease, notably in the form of SLE.  
Filgotinib has been administered in Phase 2b studies of subjects with RA and Phase 2b studies of 
subjects with CD at daily doses ranging from 50-200 mg. In general, filgotinib has been safe and 
well-tolerated in all populations studied. No clinically relevant impact on cardiovascular 
parameters (including vital signs and ECGs), respiratory or neurologic function has been
observed in trials of filgotinib. In the Phase 2b studies in RA, the most common AEs were in the 
Infections and Infestations SOC, and infections were reported more commonly in the filgotinib 
groups. Pneumonia is an identified risk for filgotinib and serious infection is considered an 
important potential risk. Reference is made to the IB for further information.
As filgotinib is an immunomodulatory agent, malignancy is closely monitored in clinical studies. 
Although an association of NHL and other malignancies with filgotinib has not been established, 
“NHL and other malignancies” is considered to be an important potential risk. Reference is made 
to the IB for further information.
Nonclinical studies in rats and dogs identified lymphoid tissues and testes as target organs for
filgotinib in long-term repeat-dose toxicity studies. Although decreased lymphocyte numbers
observed in nonclinical studies have not been seen in clinical studies, hematological assessments 
will be performed throughout the present study to ensure this potential risk is appropriately 
monitored. In both rats and dogs, microscopic findings in the testes included germ cell depletion 
and degeneration with reduced sperm content and increased cell debris in the epididymis, and 
reduced fertility in male rats. When using the AUC at the NOELs for dogs in the 26 and 39-week 
chronic toxicity studies, and in the 39-week targeted exposure toxicity study, the exposure 
margins compared with the proposed clinical dose of 200 mg once daily are 2.3, 1.8, and 
3.4-fold, respectively. Reference is made to the IB for further information about nonclinical and 
clinical testicular findings.


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GS-9876 is a highly selective SYK inhibitor with once daily dosing. Nonclinical studies show 
that SYK inhibition may have therapeutic value in the treatment of multiple autoimmune 
diseases such as RA, SLE, autoimmune cytopenias, as well as allergic and autoinflammatory 
diseases. Clinical experience with GS-9876 is limited. 
In repeat dose toxicity studies of GS-9876 (in rats for up to 26 weeks and in cynomolgus 
monkeys for up to 39 weeks), the primary observed effects were reversible, dose-dependent 
decreases in circulating lymphocytes, and decreased lymphocytes in various tissues 
(spleen, lymph nodes, thymus, and/or bone marrow), consistent with the expected pharmacology 
of SYK inhibition {Barr 2012}. Additionally, effects on erythrocyte turnover were seen in rats, 
and effects on hemostasis (hemorrhage and thrombosis) were seen in monkeys. In clinical studies 
of GS-9876 in healthy volunteers, no safety signals were identified and no grade 3 or 4 AEs were 
reported. There were no clinically significant changes in vital signs, physical findings, laboratory 
parameters, or ECGs. Given the role of SYK in platelet activation and aggregation, bleeding time 
was evaluated in the study subjects; no clinically relevant prolongation was noted. 
Filgotinib is contraindicated in pregnancy; highly effective contraception is to be used across all 
clinical studies to mitigate this risk. 
Preclinical and clinical data support the further clinical development of filgotinib and GS-9876
due to their potential benefit as novel therapies in CLE, with an acceptable level of risk 
consistent with immunomodulation in this patient population. Controlled trials will be utilized to 
minimize risk to subjects, while gaining understanding of drug efficacy. The development of 
GS-9876 and filgotinib are expected to provide valuable alternatives to existing treatments for 
CLE and related diseases. 
1.6.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is as follows:

To evaluate the efficacy of filgotinib and GS-9876 in female subjects with 
moderately-to-severely active CLE
The secondary objective of this study is as follows: 

To evaluate the safety and tolerability of filgotinib and GS-9876 in moderately-to-severely 
active CLE
The exploratory objectives of this study are as follows:
 
 
 
 
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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint of this study is:

Change from baseline in CLASI activity score from baseline to Week 12
The secondary endpoints of this study are:

Proportion of subjects at Week 12 with decrease of ≥5 points in CLASI activity score from 
baseline 

Proportion of subjects at Week 12 with no worsening in CLASI activity score from baseline 
(worsening defined as ≥3 point increase)

Proportion of subjects at Week 24 with decrease of ≥5 points in CLASI activity score from 
baseline 

Proportion of subjects at Week 24 with no worsening in CLASI activity score from baseline 
(worsening defined as ≥3 point increase)
The exploratory endpoints of this study include:
 
 
 
 
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3.2.
Study Design
This is a Phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety and 
efficacy of filgotinib and GS-9876 in female subjects with moderately-to-severely active CLE.
A schematic of this study is provided in Figure 1.
Figure 1.
Study Schema
3.3.
Study Treatments
Eligible subjects will be randomized 2:2:1 in a blinded fashion to 1 of 3 arms and receive daily 
oral doses of the following study drugs starting on Day 1 for 12 weeks: 
Arm
Study Drugs
Filgotinib 200 mg (n=20)
filgotinib 200 mg + PTM GS-9876 30 mg
GS-9876 30 mg (n=20)
GS-9876 30 mg + PTM filgotinib 200 mg
Placebo (n=10)
PTM filgotinib 200 mg + PTM GS-9876 30 mg
PTM = placebo to match
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Dayl 
Screening 
PTM 
t 
Randomization 
2:2:1 
Week 12 
1 ° Endpoint 
Week 24 
Week48 
)! 
GS-9876 30 mg+ PTM ~
,_: _G_s_-9_s_7_6_3_o_m_g_+_P_T_M ________ ~>! 
PTMgroup 
Re-randomization 
1:1 
Extension Period 
Follow Up 


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On Day 1, randomization will be stratified by two factors: (i) disease subtype (CCLE [eg DLE]
vs SCLE) and (ii) concurrent background DMARD use vs no use. 
At Week 12, upon completion of all scheduled assessments, subjects on placebo will be 
re-randomized 1:1 to receive filgotinib 200 mg + PTM GS-9876 30 mg once daily or GS-9876 
30 mg + PTM filgotinib 200 mg once daily for the remainder of the study in a blinded fashion.
Dosing and assessments for all subjects will continue through Week 24. 
Subjects who have not permanently discontinued study drug dosing in the first 24-week period 
may enter the subsequent 24-week extension period where they will continue to receive their 
assigned dose of study drug, in a blinded fashion.
3.4.
Duration of Treatment
Randomized subjects will receive a maximum of 48 weeks of study drug.
3.5.
Subject Discontinuation Criteria
3.5.1.
Study Drug Interruption Considerations
The Gilead medical monitor should be consulted prior to study drug interruption when medically 
feasible.
Study drug interruption should be considered in the following circumstances; prior to resumption 
of study drug, the investigator should discuss the case with the Gilead medical monitor:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree

Subject is scheduled for elective or emergency surgery (excluding minor skin procedures 
under local or no anesthesia); timing of study drug pausing should be determined in 
consultation with the Gilead medical monitor

If the subject has any signs or symptoms suggestive of infection (regardless of severity), 
study drug dosing should be immediately interrupted, and the medical monitor notified. Any 
subject who develops a new infection during the study should undergo prompt and complete 
diagnostic testing appropriate for an immunocompromised individual, and the subject should 
be closely monitored. Study drug should continue to be paused until the subject’s event has 
resolved, per judgment of the investigator.

Refer to Section 7.5 for details on study drug interruption due to AEs that are related to the 
study drug(s)
NOTE: During the time of study drug interruption for any of the above, the subject may continue 
to have study visits and to take part in procedures and assessments, if deemed medically 
appropriate by the investigator.


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3.5.2.
Study Drug Discontinuation Criteria
The Gilead medical monitor should be consulted prior to study drug discontinuation whenever
feasible. 
Study drug should be permanently discontinued in the following instances:

Any opportunistic infection

Any serious infection that requires antimicrobial therapy or hospitalization, or any infection 
that meets SAE reporting criteria

Complicated herpes zoster infection (with multi-dermatomal, disseminated, ophthalmic, or 
CNS involvement)

Evidence of active hepatitis C virus (HCV) during the study, as evidenced by HCV RNA 
positivity

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
subject’s ability to continue study-specific procedures or is considered to not be in the 
subject’s best interest

Subject request to discontinue for any reason

Subject noncompliance, per investigator judgment

Investigator discretion
 

Female subject becomes pregnant during the study; refer to Section 7.7.2.1

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board (IRB)/ independent ethics committee (IEC)

Subject use of prohibited concurrent therapy may trigger study drug discontinuation; 
consultation should be made with the Gilead medical monitor

Laboratory Criteria: After becoming aware of any of the following abnormal laboratory
values, study drug should be paused, and an unscheduled visit (ie, sequential visit) should 
occur to retest within 3 to 7 days (except creatinine, which should be retested 7 to 14 days 
apart). Retest may be obtained sooner if medically indicated per investigator judgment. If the 
laboratory abnormality is confirmed by the retest, then study drug should be permanently 
discontinued and further care of the subject’s CLE should be as directed per the investigator.
a) Neutrophil counts < 750 neutrophils/mm3 (SI: < 1.0 x 109 cells/L)
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b) Hemoglobin values < 8.0 g/dL (SI: < 80 g/L)
c) Platelet counts < 75,000 platelets/mm3 (SI: < 75.0 x 109 cells/L)
d) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the 
upper limit of normal range (ULN) AND total bilirubin > 2 x ULN or accompanied by 
symptoms consistent with hepatic injury
e) AST and/or ALT elevations > 3 x ULN accompanied by elevated international 
normalized ratio (INR) >1.51
f)
AST or ALT > 5 x ULN1
g) Estimated creatinine clearance (CLcr) < 40 mL/min based on the Cockcroft-Gault formula
Subjects who discontinue study drug dosing at any time may continue with study visits, 
procedures, and assessments, if deemed medically appropriate by the investigator, but will not be 
eligible for entering the 24-week extension period. Subjects who permanently discontinue study 
drug for any reason will not be replaced.
Subjects withdrawing from the study should complete the early termination (ET) and FU visits. 
Subjects are free to withdraw from the study at any time without providing reason(s) for 
withdrawal and without prejudice to further treatment. The reason(s) for withdrawal will be 
documented in the electronic case report form (eCRF). 
Reasonable efforts will be made to contact subjects who are lost to follow-up. All contacts and 
contact attempts must be documented in the subject’s file.
The sponsor has the right to terminate the study at any time in case of safety concerns or if 
special circumstances concerning the study medication or the company itself occur, making 
further treatment of subjects impossible. In this event, the investigator(s) and relevant authorities 
will be informed of the reason for study termination.
3.6.
End of Study
End of study is defined as when the last subject has completed 24 weeks of dosing (or 48 weeks 
of dosing if entering the extension period) plus the FU visit 4 weeks after the last dose of study 
drug (if applicable).
3.7.
Post Study Care
The long term care of subjects post-study will remain the responsibility of their primary treating 
physician.
                                                
1 In each case, there is a need for additional investigations, such as review of ethanol, recreational drug and dietary 
supplement consumption; testing for acute hepatitis A, B or C infection and biliary tract imaging should be promptly 
discussed with the study medical monitor.


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3.8.
Biomarker Testing
3.8.1.
Biomarker Samples to Address the Study Objectives
The following biological specimens will be collected in this study and will be used to evaluate 
the association of exploratory systemic and/or tissue specific biomarkers with study drug 
response, including efficacy and/or AEs, and to increase knowledge and understanding of the 
biology of CLE or related diseases. The specific analyses may include, but will not be limited to, 
the assays listed below.  

Plasma and serum samples for analysis of circulating factors including but not limited to 
cytokines, microRNA, and metabolites

Whole blood samples and vfPBMCs to assess cell phenotype and function

PAXgene blood samples for leukocyte gene expression analysis
 
The biomarker sample collection schedule is described in the Study Procedures Table 
(Appendix 2). Because biomarker science is a rapidly evolving area of investigation, and AEs in 
particular are difficult to predict, it is not possible to specify prospectively all tests that will be 
done on the specimens collected. The testing outlined above is based upon the current state of 
scientific knowledge. It may be modified during or after the end of the study to remove tests no 
longer indicated and/or to add new tests based upon the growing state of art knowledge. 
Specimens will be collected from all subjects. The biomarker samples will be destroyed no later 
than 15 years after the end of study. For sampling procedures, storage conditions, and shipment 
instructions, see the Sample Handling and Logistics Manual.
3.8.1.1.
Biomarker Samples for Optional Future Research
 
 
 
 
 
 
 
 
 
 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
A sufficient number of subjects will be screened to enroll approximately 50 subjects with 
moderately-to-severely active CLE.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) Female, ≥18 to ≤ 75 years of age at the time of initial written informed consent
2) Must have a diagnosis of CLE (CCLE (eg, DLE) or SCLE), per investigator evaluation, with 
the following:
a) Moderately-to-severely active CLE {Klein 2010}, with a CLASI activity score ≥10 at 
screening and Day 1
b) Prior intolerance or inadequate response (per investigator judgment) to at least one of the 
following medications for the treatment of CLE:

Topical corticosteroids or topical tacromilus, administered for ≥3 months

Oral corticosteroids ≥ 10 mg/day taken for ≥ 3 months

A conventional synthetic disease-modifying antirheumatic drug (csDMARD), 
including, but not limited to: chloroquine, quinicrine, hydroxychloroquine, 
azathioprine, mycophenolate, leflunomide, dapsone, or MTX, administered for 
≥3 months 

A bDMARD (such as belimumab or abatacept) administered for ≥3 months, or 
≥1 dose of a cell-depleting bDMARD, such as rituximab. Subjects with prior 
exposure to a B-cell depleting bDMARD (at any time) must have presence of CD19+
B cells by flow cytometry at screening
3) Subjects using antimalarials and/or topical and/or oral corticosteroids (≤10 mg prednisone)
must agree to one of the follow (a or b):
a) Continue stable doses from 28 days prior to Day 1 through Week 12 of the study
(see Section 5.6.1 for dose restrictions and other details)
b) Discontinue these medications at least 28 days prior to Day 1
4) Females of childbearing potential (as defined in Appendix 5) must have a negative pregnancy 
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5) Subjects of childbearing potential (as defined in Appendix 5) who engage in heterosexual 
intercourse must agree to use protocol specified method(s) of contraception as described in 
Appendix 5
6) Lactating subjects must agree to discontinue nursing starting from the time of written consent
through the study and for 36 days after their last dose of study drug
7) Subjects must agree not to undergo in vitro fertilization or donate their eggs for reproductive 
purposes, starting at the time of written consent through the study and for 36 days after their 
last dose of study drug
8) Meet either of the following tuberculosis (TB) screening criteria (a or b): 
a) No evidence of active or latent TB:

Negative history of TB infection and 

Negative QuantiFERON® TB-Gold In-Tube test (Note: QuantiFERON® tests with 
inconclusive results may be repeated one time. If the repeat result is also 
inconclusive, the subject is excluded from the study) and

Negative chest X-ray results (radiographs taken at Screening or within 90 days prior 
to screening with films or report available for investigator review)
b) Subjects with prior latent TB who have been treated with a full course of prophylaxis as 
per local guidelines (Note: appropriate documentation of previous treatment is required. 
In these cases, a QuantiFERON® TB-Gold In-Tube test is not needed, but a chest 
radiograph must be obtained at screening or within 3 months prior to screening [report or 
films must be available]. In addition, these cases must be approved by the Gilead medical 
monitor prior to enrollment)
NOTE: subjects with a new diagnosis of latent TB or prior untreated/partially treated latent 
TB are NOT allowed (ie, subjects who require prophylactic therapy for TB during the study).  
Subjects with current or prior active TB are excluded (regardless of treatment).
9) Are able and willing to sign the informed consent as approved by the IRB/IEC. Written 
consent must be provided before initiating any screening evaluations. Subjects must have 
read and understood the ICF, must fully understand the requirements of the study, and must 
be willing to comply with all study visits and assessments; subjects who cannot read or 
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4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Have active SLE or Sjogren’s syndrome (SjS) that requires use of a prohibited medication
(refer to Section 5.6.2). Systemic lupus erythematosus or SjS that is readily managed with 
protocol-permitted medications is allowed, per investigator judgment
2) Have another highly active inflammatory/autoimmune/rheumatic disease (such as highly 
active RA, nephritis, or CNS inflammation) which would compromise subject safety or 
interfere with the conduct of the study (per investigator judgment). Stable conditions, 
eg, stable thyroiditis, are permitted
3) Previous dosing within 3 months of screening with a JAK inhibitor or SYK inhibitor
(marketed or investigational)
4) Previous history of cyclophosphamide use (at any time)
5) Known hypersensitivity to the study drugs, their metabolites, or formulation excipients
6) Major surgery (requiring regional block or general anesthesia) within 30 days prior to 
screening, or planned during the study
7) Active infection that is clinically significant, per investigator judgment, or any infection 
requiring hospitalization or treatment with intravenous anti-infectives within 60 days prior to
screening; or any infection requiring oral anti-infective therapy within 30 days prior to
screening
8)
Subjects who are pregnant, breastfeeding, or planning to become pregnant or breastfeed 
during the study or for 36 days after their last dose of study drug
9) A positive test result for human immunodeficiency virus (HIV)-1 and 2 antibody at or prior 
to screening
10) Positive for HCV antibodies at screening. Subjects with positive HCV antibody (Ab) will 
require reflex testing for HCV RNA. Subjects with positive HCV RNA viral load (VL) at 
screening will be excluded. Subjects with positive HCV Ab, but negative HCV RNA VL are 
eligible per investigator judgment, but require ongoing monitoring as outlined in the schedule 
of assessments 
11) Positive for hepatitis B surface antigen (HBsAg) or HBV core antibodies at screening
(regardless of HBV VL)
12) History of malignancy within the last 5 years prior to screening (except for successfully
treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin or 
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13) History of lymphoproliferative disorder or current lymphoproliferative disease
14) History of organ or bone marrow transplant
15) Use of prohibited concomitant medications per Section 5.6.2
16) Any chronic, uncontrolled medical condition which would put the subject at increased risk 
during study participation, such as uncontrolled: diabetes, hypertension, morbid obesity, 
thyroid, adrenal, pulmonary, hepatic, renal, neurologic or psychiatric disease, or other disease 
of concern, as per judgment of investigator 
17) Administration of a live/attenuated vaccine within 4 weeks prior to Day 1, or planned during 
the study or for 12 weeks after subject’s last dose of study drug
18) History of opportunistic infection or immunodeficiency syndrome, which would put the 
subject at risk, per investigator judgment
19) Currently on systemic (oral or intravenous) anti-infective therapy for chronic infection 
(such as pneumocystis [PCP], cytomegalovirus [CMV], Herpes zoster, and atypical 
mycobacteria). Past history of disseminated Staphyloccoccus aureus or disseminated Herpes 
simplex infection
20) History of symptomatic Herpes zoster or herpes simplex within 12 weeks of screening, or 
any history of disseminated Herpes simplex, Herpes zoster, ophthalmic zoster, or central 
nervous system zoster
21) Blood loss, donation (> 500 mL), or blood product transfusion within 12 weeks of Day 1
22) Known bleeding disorder or hypercoagulable state; antiphospholipid antibody (APLA) 
syndrome with prior clinically significant event (per judgment of investigator); or on chronic 
anticoagulation/anti-platelet therapy such as warfarin, heparin, etc, as outlined in 
Section 5.6.2 (NOTE: stably prescribed chronic aspirin therapy ≤325 mg/day for 
cardiovascular prophylaxis is allowed)
23) Current drug or alcohol abuse, per judgment of investigator
24) Any condition or circumstances which in the opinion of the investigator may make a subject 
unlikely or unable to complete the study or comply with study procedures and requirements
25) Participation in any clinical study of an investigational drug within 4 weeks or 5 half-lives 
prior to screening, whichever is longer. Exposure to investigational biologics should be 
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26) Tests performed at the central laboratory at screening that meet any of the criteria below 
(at the investigator’s discretion, out of range lab values may be retested one time to rule out 
laboratory error):
i)
Hemoglobin < 8.0 g/dL (International System of Units [SI]: < 80 g/L);
ii) Absolute neutrophil count (ANC) < 1.5 x 103 cells/mm3 (SI: < 1.5 x 109 cells/L);
iii) Platelet count < 100 x 103 cells/mm3 (SI: < 100 x 109 cells/L);
iv) ALT or AST ≥1.5 x upper limit of normal ULN;
v) Total bilirubin level ≥ 2 x ULN unless the subject has a diagnosis of Gilbert’s disease 
with clear documentation
vi) Estimated CLcr < 60 mL/min based on the Cockcroft-Gault equation.
4.4.
Screen Failures
Subjects who do not meet eligibility criteria for study entry (“screen failures”) may be rescreened 
one time in select cases. For example,

To adequately washout a concomitant medication

Administrative reasons (eg, exceeding the screening window due to issues with appointment 
scheduling or obtaining results of laboratory data)
Written approval must be obtained from the sponsor prior to rescreening. Rescreening may not 
be used to recheck a subject who is likely unsuitable for the study (for example, to check whether 
a chronically abnormal laboratory test is closer to normal range). 
Subjects who are permitted to rescreen must repeat the informed consent process and sign a new 
informed consent form. A new screening number will be assigned. The following test/procedure
will not need to be repeated (unless required per investigator judgment) if results are available 
within the appropriate timeframe:

Chest x-ray, if performed within 3 months prior to the rescreening visit


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding and Treatment Codes
An Interactive Web Response System (IWRS) will be employed to manage subject 
randomization and treatment assignments. It is the responsibility of the investigator to ensure that 
the subject is eligible for the study prior to enrollment. Subjects will be assigned a screening 
number at the time of consent. 
5.1.1.
Procedures for Breaking Treatment Codes
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject, the investigator may obtain treatment assignment directly from the IWRS system 
for that subject. Gilead recommends but does not require that the investigator contact the 
Gilead medical monitor before breaking the blind. Treatment assignment should remain blinded 
unless that knowledge is necessary to determine subject emergency medical care. The rationale 
for unblinding must be clearly explained in source documentation and on the eCRF, along with 
the date on which the treatment assignment was obtained. The investigator is requested to 
contact the Gilead medical monitor promptly in case of any treatment unblinding.
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a 
subject’s treatment assignment is disclosed to the investigator, the subject will have study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject.
Gilead Drug Safety and Public Health (DSPH) may independently unblind cases for expedited 
reporting of suspected unexpected serious adverse reactions (SUSARs).
5.2.
Description of Filgotinib and PTM Filgotinib
5.2.1.
Formulation of Filgotinib and PTM Filgotinib
Filgotinib 200 mg tablets are beige, debossed with “GSI” on one side and “200” on the other, 
capsule-shaped, film-coated tablets for clinical use. Each tablet contains the equivalent of 
200 mg filgotinib free base in the form of filgotinib maleate. In addition to the active ingredient, 
filgotinib tablets contain the following inactive ingredients: microcrystalline cellulose, lactose 
monohydrate, fumaric acid, pregelatinized starch, silicon dioxide, magnesium stearate, 
macrogol/PEG 3350, polyvinyl alcohol, talc, titanium dioxide, iron oxide yellow, and iron oxide 
red. 
Placebo to match filgotinib 200 mg tablets are identical to the active tablets in appearance. 
Placebo to match filgotinib 200 mg tablets contains the following inactive ingredients: 
microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, 
macrogol/PEG 3350, polyvinyl alcohol, talc, titanium dioxide, iron oxide yellow, and iron oxide 
red.


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5.2.2.
Packaging and Labeling of Filgotinib and PTM Filgotinib
Filgotinib and PTM filgotinib tablets are packaged in white, high density polyethylene (HDPE) 
bottles. Each bottle contains 30 tablets, silica gel desiccant and polyester packing material. Each 
bottle is enclosed with a white, continuous thread, child-resistant polypropylene screw cap fitted 
with an induction-sealed, aluminum-faced liner.
Study drugs to be distributed to centers in North America shall be labeled to meet applicable 
requirements of the United States Food and Drug Administration (FDA) and/or other local 
regulations as applicable.
5.3.
Description of GS-9876 and PTM GS-9876
5.3.1.
Formulation of GS-9876 and PTM GS-9876
GS-9876 will be supplied as 30 mg tablets that are round, plain-faced and film-coated blue. Each 
tablet contains 30 mg of GS-9876 free base as the succinate form (GS-9876-02). The GS-9876 
tablets contain commonly used excipients including microcrystalline cellulose, mannitol, 
croscarmellose sodium, magnesium stearate, polyvinyl alcohol, polyethylene glycol, titanium 
dioxide, talc, and FD&C blue #2/indigo carmine aluminum lake. 
Placebo to match tablets will be supplied that are identical in physical appearance to the 
GS-9876 30 mg tablets and contain the following inactive ingredients: microcrystalline cellulose, 
lactose monohydrate, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, 
polyethylene glycol, titanium dioxide, talc, and FD&C blue #2/indigo carmine aluminum lake.
5.3.2.
Packaging and Labeling of GS-9876 and PTM GS-9876
GS-9876 and PTM GS-9876 tablets are packaged in white, HDPE bottles. Each bottle contains 
30 tablets, silica gel desiccant and polyester packing material. Each bottle is enclosed with a 
white, continuous thread, child-resistant polypropylene screw cap with an induction-sealed,
aluminum-faced liner.
Study drug(s) to be distributed to centers in North America will be labeled to meet applicable 
requirements of the FDA and/or other local regulations.
5.4.
Storage and Handling of Study Drugs
Filgotinib, PTM filgotinib, GS-9876, and PTM GS-9876 tablets should be stored at controlled 
room temperature of 25 ºC (77 ºF); excursions are permitted between 15 ºC and 30 ºC (59 ºF and 
86 ºF). Storage conditions are specified on the label. 
Until dispensed to the subjects, all drug products should be stored in a securely locked area, 
accessible only to authorized site personnel. To ensure the stability of the study drugs and to 
ensure proper product identification, the drug products should not be stored in a container other 
than the containers in which they are supplied. Consideration should be given to handling, 
preparation, and disposal through measures that minimize drug contact with the body. 
Appropriate precautions should be followed to avoid direct eye contact or exposure when 
handling.


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5.5.
Dosage and Administration of Study Drugs
Study drugs will be administered once daily with or without food. Each subject should be given 
instructions to maintain approximately the same daily time of administration to ensure a similar 
dosing interval between study drug doses. 
For missed dose(s) of study medication, subjects should be instructed to take the missed dose(s) 
of study medication as soon as possible during the same day. If the missed dose is not taken on 
the original day, subjects should be cautioned not to double the next dose with the missed dose of 
study drug under any circumstances. In those cases, the missed dose should be returned to the 
study drug bottle.
5.6.
Prior and Concomitant Medications
All medications taken for the treatment of CLE will be recorded in the source documents and on
the eCRF. All other medications (for non-CLE indications) taken up to 30 days prior to the 
screening visit through the end of the study (4 weeks after the last dose of study drug) will be 
recorded in the source documents and on the eCRF. At each study visit, the study center will 
capture any and all medications taken by the subject since the last visit or during the visit 
(as applicable). Concomitant medications include prescription and non-prescription medications, 
dietary supplements, vitamins, and minerals.
Effective current therapies should not be discontinued for the sole purpose of participating in this 
study. Subjects may receive medications to treat AEs as deemed necessary by the investigator or 
the subject’s health care providers. Should subjects have a need to initiate treatment with any 
excluded concomitant medication, the Gilead medical monitor should be consulted prior to 
initiation of the new medication, where possible. In instances where an excluded medication is 
initiated prior to discussion with the sponsor, the investigator must notify Gilead as soon as 
he/she is aware of the use of the excluded medication.
5.6.1.
Allowed Concomitant Medications 
5.6.1.1.
Concomitant Medications for CLE
The allowed concomitant medication(s) for CLE should be maintained, as much as possible, at
stable doses (defined as no change in prescription) 28 days prior to Day 1 through Week 12:

Class V-VII topical corticosteroids for CLE as listed below (administered per investigator 
judgment). If the investigator wishes to use a Class V-VII topical corticosteroid not listed 
below, the investigator should obtain approval from the Gilead medical monitor prior to 
initiation of the medication, where possible
Alclometasone dipropionate up to 0.05% concentration
Desonide up to 0.05% concentration
Fluocinolone acetonide up to 0.03% concentration
Fluticasone propionate up to 0.05% concentration


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Hydrocortisone acetate up to 2.5% concentration
Hydrocortisone probutate up to 0.1% concentration
Hydrocortisone valerate up to 0.2% concentration

Oral corticosteroids for CLE ≤ 10 mg prednisone/day (or equivalent). Subjects who are not 
planning to continue oral corticosteroids during the study must have discontinued them at 
least 28 days prior to Day 1

Oral antimalarials (eg, chloroquine ≤ 250 mg/day, hydroxychloroquine ≤400 mg/day, or 
quinacrine ≤ 100 mg/day) for CLE (administered per investigator judgment). Subjects who 
are not planning to continue oral antimalarials during the study must have discontinued them 
at least 28 days prior to Day 1

Oral dapsone ≤ 100 mg/day. Subjects who are not planning to continue dapsone during the 
study must have discontinued the drug at least 28 days prior to Day 1  

Oral or injectable MTX ≤ 20 mg per week (subjects on MTX should also be on folic acid 
supplementation [or equivalent], per local standard of care). All local standard-of-care 
practices for the administration of MTX, including laboratory testing, follow-up care, and 
contraindications should be performed throughout the study. The concomitant use of 
medicines which may increase the risk of hepatotoxicity and/or nephrotoxicity with MTX 
(such as NSAIDs, salicylates, or other folate antagonists) should be avoided, as much as 
possible, in accordance with clinical practice
After completion of the Week 12 visit, the dose and/or frequency of these medications may be 
reduced one or more times per investigator judgment. In these cases, the dose and/or frequency 
may be increased again as needed, but should not exceed the subject’s Day 1 dose and frequency.
Subjects who require concomitant medications at doses and/or frequencies that are higher than 
their Day 1 dose for ≥ 14 consecutive days are to be withdrawn from study drug but may 
continue with study visits per investigator judgment.
Dose adjustment for toxicity management is allowed at any time. A toxicity requiring dose 
adjustment should be reported as an AE or SAE and managed as outlined in Section 7.5.
5.6.1.2.
Other Concomitant Medications
The following concomitant medications should be maintained, as much as possible, at stable 
prescription for at least 28 days prior to Day 1 and throughout the duration of the study.

Cevilimine or pilocarpine, as prescribed by investigator

Azathioprine up to a maximum of 2 mg/kg bodyweight/day or 300 mg/day, whichever is 
lower

Vitamins, minerals, and herbal supplements

Hormonal contraceptives or female hormone replacement therapy


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
Other chronic therapies including, but not limited to, antihypertensives, thyroid replacement, 
analgesics, daily aspirin for cardiovascular prophylaxis (≤ 325 mg/day), and chronic 
nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics
5.6.2.
Prohibited Concomitant Medications 
The prohibited medications are as follows:
Table 2.
Prohibited Medications
Drug Class
Agents Disallowed
Prohibited Period
Biologic
Immunomodulator
Anti-tumor necrosis factor drugs
infliximab, adalimumab, belimumab, 
golimumab, certolizumab, rituximab
(CD19+ B cells must be present),
dupilumab, or biosimilar agent
(if applicable)
90 days prior to screening through the 
end of study participation
Any other investigational
immunomodulatory biologic agent or 
biosimilar (if applicable)
90 days or 5 half-lives prior to screening 
(whichever is longer) through the end of 
study participation
Prohibited CLE Medications
Corticosteroids
Oral corticosteroids > 10 mg prednisone
equivalent/day
28 days prior to Day 1 through the end 
of study participation
Injectable corticosteroids
28 days prior to Day 1 through the end 
of study participation
Class I-IV topical corticosteroids
28 days prior to Day 1 through the end 
of study participation
Non-biologic
Immunomodulator
Azathioprine (> 2 mg/kg bodyweight/day 
or 300 mg/day, whichever is lower), 
colchicine, cyclosporine, dapsone (>100 
mg/day), tacrolimus (oral or topical), gold 
salts, minocycline, MTX > 20 mg/week
(subcutaneous or oral), mycophenolate, 
penicillamine, sirolimus or other 
immunomodulatory/immunosuppressive 
therapies (with the exception of oral 
antimalarials as permitted in 
Section 5.6.1.1)
28 days prior to Day 1 through the end 
of study participation
Strong P-gp Inducersa
Anticonvulsants
Phenobarbital, phenytoin, or 
carbamazepine
21 days prior to Day 1 through the end 
of study participation
Antimycobacterials
Rifabutin, rifapentine, rifampin
Herbal/Natural 
Supplements
St. John’s wort or danshen 
(salvia miltiorrhiza)


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Drug Class
Agents Disallowed
Prohibited Period
CYP3A4 Inhibitorsb
Strong CYP3A4 
Inhibitors
Clarithromycin, conivaptan, itraconazole, 
ketoconazole, nefazodone, posaconazole, 
telithromycin, voriconazole, telaprevir, 
boceprevir, grapefruit juice, idelalisib, 
Viekira Pak (ombitasvir, paritaprevir, 
ritonavir, dasabuvir), troleandomycin, or
mibefradil
14 days prior to Day 1 through the end 
of study participation
Moderate CYP3A4 
Inhibitors
Fluconazole, erythromycin, diltiazem, 
dronedarone, aprepitant, casopitant, 
imatinib, verapamil, tofisopam, 
ciprofloxacin, cimetidine, cyclosporine, 
Schisandra sphenanthera, crizotinib, 
netupitant, nilotinib, or isavuconazole
14 days prior to Day 1 through the end 
of study participation
CYP3A4 Inducersc
Strong CYP3A4 Inducers
Carbamazepine, phenytoin, rifampin, 
fosphenytoin, pentobarbital, primidone, 
rifabutin, rifapentine, phenobarbital, 
mitotane, avasimibe, St. John’s Wort, 
enzalutamide
14 days prior to Day 1 through the end 
of study participation
Moderate CYP3A4 
Inducers
Bosentan, thioridazine, nafcillin, modafinil, 
semagacestat, genistein
14 days prior to Day 1 through the end 
of study participation
Other
JAK Inhibitor
Ruxolitinib or tofacitinib
(or investigational)
3 months prior to screening through the 
end of study participation
SYK Inhibitor
Fostamatinib or entospletinib
(or investigational)
3 months prior to screening through the 
end of study participation
Anti-platelet
Adenosine diphosphate (ADP) receptor 
inhibitors, phosphodiesterase inhibitors, 
PAR-1 antagonists, glycoprotein 2b/3a 
inhibitors
One year prior to screening through the 
end of study participation
Aspirin > 325 mg/day
14 days prior to Day 1 through the end 
of study participation
Anti-coagulant
Warfarin, any Vitamin K antagonist, any 
novel oral anticoagulant, any heparin or 
low molecular heparins, or inhibitors of 
factor Xa
One year prior to screening through the 
end of study participation
a
May result in a decrease in the concentrations of filgotinib. Filgotinib is a P-gp substrate. A single dose of 200 mg 
itraconazole (a potent P-gp inhibitor) increased filgotinib Cmax by 63.9% and AUCinf by 44.6% but had no effect on the 
major, active metabolite GS-829845.
b
May result in an increase in the concentrations of GS-9876
c
May result in a decrease in the concentrations of GS-9876


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5.7.
Vaccine Guidelines
Prior to study participation, it is recommended that the subject’s vaccinations be brought up to 
date according to local vaccination standards.
Live or attenuated vaccines (including, but not limited to varicella and inhaled flu vaccine) are 
prohibited within 4 weeks of Day 1, throughout the study, and for 12 weeks after the last dose of 
study drug.
Subjects should be advised to avoid routine household contact with persons vaccinated with 
live/attenuated vaccine components. General guidelines suggest that a study subject’s exposure 
to household contacts should be avoided for the below stated time periods:

Varicella or attenuated typhoid fever vaccination – avoid contact for 4 weeks following 
vaccination

Oral polio vaccination - avoid contact for 6 weeks following vaccination

Attenuated rotavirus vaccine - avoid contact for 10 days following vaccination

Inhaled flu vaccine - avoid contact for 1 week following vaccination
Inactivated vaccines (such as inactivated flu vaccines) should be administered according to local 
vaccination standards whenever medically appropriate; however, there are no available data on 
the concurrent use of filgotinib or GS-9876 and their impact on immune responses following 
vaccination.
5.8.
Accountability of Study Drugs
The investigator is responsible for ensuring adequate accountability of all used and unused study 
drug. This includes acknowledgement of receipt of each shipment of study drug (quantity and 
condition). All used and unused study drug dispensed to subjects must be returned to the site.
Study drug accountability records will be provided to each study site to:

Record the date received and quantity of study drug

Record the date, subject number, subject initials, the study drug number dispensed

Record the date, quantity of used and unused study returned, along with the initials of the 
person recording the information.
5.8.1.
Study Drug Return or Disposal
For additional information about study drug accountability, return, and disposal, refer to 
Section 9.1.7.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows. Additional information is 
provided in the study procedures manual.
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
Subject eligibility will be established at the conclusion of the screening evaluations. The 
screening number and subject ID will be assigned for each subject by IWRS. 
It is the responsibility of the investigator to ensure that each subject is eligible for the study 
before randomization. A subject will be considered enrolled once they have been randomized.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened up to 28 days prior to randomization (Day 1) to determine eligibility 
for participation in the study. 
The following will be performed and documented at screening:

Obtain written informed consent

Review of inclusion/exclusion criteria

Obtain medical history (including demographics, surgical history, and CLE history with 
documentation of prior skin biopsy results, if available)

Complete PE

Height

Weight

Vital signs (blood pressure, heart rate, respiratory rate, and temperature)

PGA

CLASI

Standard 12-lead ECG

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)


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Endocrine Tests (HbA1c and TSH)
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
Serum Pregnancy Test (for females of childbearing potential) or FSH test (for females of 
nonchildbearing potential)
Virology Tests (HIV-1, HIV-2, HBV, and HCV)
QuantiFERON® TB Gold in Tube Test (if applicable)
Biomarker Samples
o
Whole Blood, Cytochex
o
Whole Blood, Heparin
o
Serum and plasma biomarker samples
o
vfPBMC sample
o
PAXgene RNA sample

Obtain urine samples for:
Urinalysis
Urine Drug and Alcohol test
Urine protein to creatinine ratio

Chest x-ray (if not obtained within 3 months prior to screening, with films or report available 
for investigator review)
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic for randomization into the study on Day 1.
Subjects who do not meet the eligibility criteria will be excluded from randomization and may be 
considered for rescreening one time for the study in consultation with the sponsor or its designee.
Refer to Section 4.4 for additional details.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all SAEs, as well as any AEs related to protocol-mandated procedures 
on the AE eCRF and any concomitant medications in the concomitant medication eCRF. All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. 
See Section 7.6 Adverse Events and Toxicity Management for details.
6.2.2.
Day 1 Assessments
Day 1 assessments, including study drug administration, will be done at the study center. The 
following will be performed and documented prior to dosing:

Updates to medical history 


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
Weight

Symptom-driven physical examination

Vital signs (blood pressure, heart rate, respiratory rate, and temperature)

PGA

CLASI

Detailed target lesion assessment (see Section 6.9.2.3 for details)

Photographs of areas with skin involvement (identifying subject features should be obscured, 
as much as possible)

Detailed mucous membrane assessment (see Section 6.9.2.4 for details)

Subject questionnaires:
Subject’s global assessment of CLE disease activity
Subject assessment of autoimmune disease-related dry eyes/mouth
Subject assessment of autoimmune disease-related body pain
Subject assessment of autoimmune disease-related joint pain/stiffness
Subject assessment of autoimmune disease-related fatigue
Subject assessment of CLE on sexual activity
SF-36
DLQI
TSQM

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)
Fasting lipids (overnight fast [no food or drinks, except water] of at least 8 hours required 
prior to blood sample collection)
CRP and ESR
Quantitative Serum Immunoglobulin Test
Autoantibody Panel and Complement Levels


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Biomarker Samples (predose) 
o
Whole Blood, Cytochex
o
Whole Blood, Heparin
o
Serum and plasma biomarker samples
o
vfPBMC sample
o
PAXgene RNA sample

Obtain urine sample for:
Urinalysis
Urine pregnancy test (for females of childbearing potential)
Urine protein to creatinine ratio

After the subject’s eligibility for the study has been confirmed, the subject will be 
randomized to 1 of 3 arms

Study drug dispensation

Review and record all adverse events and concomitant medications
6.3.
Randomization
Upon qualification for the study, subjects will be randomized in a 2:2:1 ratio using a 
computerized IWRS system on the Day 1 visit. 
For each subject at each dispensation visit, the clinic will contact the IWRS system for the 
appropriate kit number to be dispensed. The kit will contain the relevant study drug for the 
period until the next dispensation visit.
Refer to Sections 3.3 and Section 6.1 for additional details.
6.4.
Week 2 through Week 24 (Study Dosing Period)
The following assessments will be completed as specified in the Study Procedures 
Table (Appendix 2). 

Weight
CCI
CCII 


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
Symptom-driven physical examination

Vital signs (blood pressure, heart rate, respiratory rate, and temperature)

PGA

CLASI

Detailed target lesion assessment (see Section 6.9.2.3 for details)

Photographs of areas with skin involvement (identifying subject features should be obscured, 
as much as possible)

Detailed mucous membrane assessment (Weeks 2, 12, 14, and 24; see Section 6.9.2.4 for 
details)

Subject questionnaires:
Subject’s global assessment of CLE disease activity
Subject assessment of autoimmune disease-related dry eyes/mouth
Subject assessment of autoimmune disease-related body pain
Subject assessment of autoimmune disease-related joint pain/stiffness
Subject assessment of autoimmune disease-related fatigue
Subject assessment of CLE on sexual activity
SF-36
DLQI
TSQM

Standard 12-lead ECG (Week 24 only)

HCV monitoring (Weeks 12 and 24; if applicable)

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)
Fasting Lipids (Weeks 12 and 24; overnight fast [no food or drinks, except water] of at 
least 8 hours required prior to blood sample collection)
CRP and ESR
Quantitative Serum Immunoglobulin Test (Weeks 8 and 20)
Autoantibody Panel and Complement Levels (Weeks 12 and 24)


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Biomarker Samples (Weeks 2, 4, 12, and 24)
o
Whole Blood, Cytochex
o
Whole Blood, Heparin
o
Serum and plasma biomarker samples
o
vfPBMC sample
o
PAXgene RNA sample
Pharmacokinetic Samples (Week 2 [at least 30 minutes and up to 3 hours after 
dosing],Week 4 [anytime], Week 12 [within 2 hours prior to study drug administration], 
and Week 24 [within 2 hours prior to study drug administration])

Obtain urine sample for:
Urinalysis
Urine pregnancy test (for females of childbearing potential)
Urine protein to creatinine ratio
 

Re-randomization 1:1 upon completion of Week 12 assessments (subjects on placebo only, 
will be performed in a double-blind fashion via IWRS)

Study drug dispensation (not applicable at Weeks 2 and 14 and not applicable at Week 24 for 
subjects who do not enter the 24-week extension period)

Study drug accountability

Review and record all adverse events and concomitant medications
6.5.
Week 30 through Week 48 (24-week Extension Period)
The following assessments will be completed at each visit or as specified. All assessments are 
summarized in the Study Procedures Table (Appendix 2). 

Weight

Symptom-driven physical examination

Vital signs (blood pressure, heart rate, respiratory rate, and temperature)

PGA
CCII 


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
CLASI

Detailed target lesion assessment (see Section 6.9.2.3 for details)

Photographs of areas with skin involvement (identifying subject features should be obscured, 
as much as possible)

Detailed mucous membrane assessment (Weeks 36 and 48; see Section 6.9.2.4 for details)

Subject questionnaires:
Subject’s global assessment of CLE disease activity
Subject assessment of autoimmune disease-related dry eyes/mouth
Subject assessment of autoimmune disease-related body pain
Subject assessment of autoimmune disease-related joint pain/stiffness
Subject assessment of autoimmune disease-related fatigue
Subject assessment of CLE on sexual activity
SF-36
DLQI
TSQM

Standard 12-lead ECG (Weeks 36 and 48)

HCV monitoring (Weeks 36 and 48; if applicable)

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)
Fasting Lipids (Week 42 only; overnight fast [no food or drinks, except water] of at least 
8 hours required prior to blood sample collection)
CRP and ESR
Quantitative Serum Immunoglobulin Test (Week 42 only)
Autoantibody Panel and Complement Levels (Week 42 only)
Biomarker Samples (Week 48 only)
o
Serum and plasma biomarker samples
o
PAXgene RNA sample

Obtain urine sample for:
Urinalysis


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Urine pregnancy test (for females of childbearing potential). When visits are greater than 
4 weeks apart, women should continue to have urine pregnancy tests every 4 weeks using 
at home pregnancy test kits that will be provided to them. The site will call the subject 
every 4 weeks to obtain results of these pregnancy tests and will record the information in 
the source documents and eCRF. If any urine pregnancy test is positive, study drug 
should be immediately interrupted and the subject should return to the study center for a 
serum pregnancy test
Urine protein to creatinine ratio

Study drug dispensation (not applicable at Week 48)

Study drug accountability

Review and record all adverse events and concomitant medications
6.6.
Follow-up Assessments
A FU visit will be conducted 4 weeks after the last dose of study drug. Subjects who discontinue 
study drug ≥ 4 weeks prior to their last visit will not be asked to return for a FU visit. 

Weight

Symptom-driven physical examination

Vital signs (blood pressure, heart rate, respiratory rate, and temperature)

PGA

CLASI

Detailed target lesion assessment (see Section 6.9.2.3 for details)

Photographs of areas with skin involvement (identifying subject features should be obscured, 
as much as possible)

Subject questionnaires:
Subject’s global assessment of CLE disease activity
Subject assessment of autoimmune disease-related dry eyes/mouth
Subject assessment of autoimmune disease-related body pain
Subject assessment of autoimmune disease-related joint pain/stiffness
Subject assessment of autoimmune disease-related fatigue
Subject assessment of CLE on sexual activity


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SF-36
DLQI

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)
Complement Levels
Biomarker Samples 
o
Serum and plasma biomarker samples
o
PAXgene RNA sample

Obtain urine sample for:
Urinalysis
Urine pregnancy test (for females of childbearing potential)
Urine protein to creatinine ratio

Review and record all adverse events and concomitant medications
6.7.
Early Termination Assessments
Subjects who discontinue the study prior to Week 24 (or prior to Week 48 for subjects entering 
the 24-week extension period) will return to the study center for the ET visit.

Weight

Symptom-driven physical examination

Vital signs (blood pressure, heart rate, respiratory rate, and temperature)

PGA

CLASI

Detailed target lesion assessment (see Section 6.9.2.3 for details)

Photographs of areas with skin involvement (identifying subject features should be obscured, 
as much as possible)

Subject questionnaires:
Subject’s global assessment of CLE disease activity


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Subject assessment of autoimmune disease-related dry eyes/mouth
Subject assessment of autoimmune disease-related body pain
Subject assessment of autoimmune disease-related joint pain/stiffness
Subject assessment of autoimmune disease-related fatigue
Subject assessment of CLE on sexual activity
SF-36
DLQI
TSQM

Standard 12-lead ECG (if not completed within the prior 12 weeks)

HCV monitoring (if applicable, if not completed within the prior 12 weeks)

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)
CRP and ESR
Complement Levels 
Biomarker Samples 
o
Whole Blood, Cytochex
o
Whole Blood, Heparin
o
Serum and plasma biomarker samples
o
vfPBMC sample
o
PAXgene RNA sample

Obtain urine sample for:
Urinalysis
Urine pregnancy test (for females of childbearing potential)
Urine protein to creatinine ratio

Study drug accountability

Review and record all adverse events and concomitant medications


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6.8.
Unscheduled Visit Assessments
A subject should attend an unscheduled visit if requested by the sponsor or the investigator. The 
assessments performed are at the investigator’s discretion.
6.9.
Study Assessments
6.9.1.
Priority of Assessments
Subject-reported outcomes are recommended to be completed before any other study procedures. 
Invasive study procedures such as blood draws and biopsies should be done at the end of a study 
visit, as much as possible. Investigator questionnaires/assessments should be performed prior to 
reviewing subject-reported outcomes for that visit, as much as possible. 
6.9.2.
Efficacy
Efficacy assessments will be performed at the time points indicated in the Study Procedures 
Table (Appendix 2).
6.9.2.1.
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)
The CLASI is assessed using a one-page tool which lists each part of the body separately and 
results in separate scores for skin damage and disease activity.  
6.9.2.2.
Physician’s Global Assessments of CLE Disease Activity
The Physician’s Global Assessment of CLE Disease Activity will be recorded on a 0-100 mm 
visual analogue scale (VAS; Appendix 7), with 0 indicating “no CLE disease activity” and 
100 indicating “maximum CLE disease activity”. The evaluating physician and the subject 
should complete the global assessments independently of each other.
6.9.2.3.
Detailed Target Lesion Assessments
The investigator will identify a highly clinically active lesion on Day 1. The lesion will be 
measured and assessed for edema (0 = absent, 1 = slight, just palpable, 2 = visible and palpable).
The area that was assessed will be recorded in the source documents.
6.9.2.4.
Detailed Mucous Membrane Assessments
Mucous membranes will be assessed for lesions at the buccal mucosa, the hard and soft palates, 
and the nasal mucosal areas for erythema, keratosis, and erosions and scored as indicated below.
Area of Lesion Assessment
Erythema
Keratosis
Erosions
Buccal Mucosa
0 = absent
1 = present
0 = absent
1 = present
0 = absent
1 = erosion
2 = ulceration
Hard and Soft Palates
0 = absent
1 = present
0 = absent
1 = present
0 = absent
1 = erosion
2 = ulceration
Nasal Mucosal Areas
0 = absent
1 = present
0 = absent
1 = present
0 = absent
1 = erosion
2 = ulceration


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6.9.2.5.
Subject’s Global Assessment of CLE Disease Activity
The Subject’s Global Assessment of CLE Disease Activity will be recorded on a 0-100 mm 
VAS, with 0 indicating “I have no CLE” and 100 indicating “I have the worst CLE.”
6.9.2.6.
Subject Assessment of Autoimmune Disease-Related Dry Eyes/Mouth
The Subject Assessment of Autoimmune Disease-Related Dry Eyes/Mouth will be recorded on a 
0-100 mm VAS (Appendix 8), with 0 indicating “I have no dry eye/mouth due to my 
autoimmune condition” and 100 indicating “I have the worst dry eye/mouth due to my 
autoimmune.”
6.9.2.7.
Subject Assessment of Autoimmune Disease-Related Body Pain
The Subject Assessment of Autoimmune Disease-Related Body Pain will be recorded on a 
0-100 mm VAS (Appendix 8), with 0 indicating “I have no body pain due to my autoimmune 
condition” and 100 indicating “I have the worst body pain due to my autoimmune condition.”
6.9.2.8.
Subject Assessment of Autoimmune Disease-Related Join Pain/Stiffness
The Subject Assessment of Autoimmune Disease-Related Joint Pain/Stiffness will be recorded 
on a 0-100 mm VAS (Appendix 8), with 0 indicating “I have no joint pain/stiffness due to my 
autoimmune condition” and 100 indicating “I have the worst joint pain/stiffness due to my 
autoimmune condition.”
6.9.2.9.
Subject Assessment of Autoimmune Disease-Related Fatigue
The Subject Assessment of Autoimmune Disease-Related Fatigue will be recorded on a 
0-100 mm VAS (Appendix 8), with 0 indicating “I have no fatigue due to my autoimmune 
condition” and 100 indicating “I have the worst fatigue due to my autoimmune condition.”
6.9.2.10.
Subject Assessment of CLE on Sexual Activity
The Subject Assessment of CLE on Sexual Activity will be recorded on a 0-100 mm VAS 
(Appendix 8), with 0 indicating “my CLE does not affect my sexual activity” and 100 indicating 
“my CLE completely stops my sexual activity.”
6.9.2.11.
36-Item Short Form Healthy Survey
The SF-36 is a health related quality of life instrument consisting of 36 questions belonging to 
8 domains in 2 components and covers a 4-week recall period:

Physical well-being, 4 domains: physical functioning (10 items), role physical (4 items), 
bodily pain (2 items), and general health perceptions (5 items)

Mental well-being, 4 domains: vitality (4 items), social functioning (2 items), role emotional 
(3 items), and mental health (5 items).


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The remaining item (health transition) is not part of the above domains but is kept separately. 
These scales will be rescaled from 0 to 100 (converting the lowest possible score to 0 and the 
highest possible score to 100), with higher scores indicating a better quality of life. The SF-36 is 
not disease specific and has been validated in numerous health states.
6.9.2.12.
Dermatology Quality of Life Index (DLQI)
The DLQI is a 10-question questionnaire used to measure the impact of skin disease on the 
quality of life of an affected person. Subjects will assess the impact of skin disease based on the 
previous week. Dermatology Quality of Life Index topics include symptoms and feelings, daily 
activities, leisure, work and school, personal relationships, and treatment. Each question is 
scored from 0 to 3 (0 = not at all, not relevant, or question unanswered; 1 = a little, 2 = a lot, 
3 = very much).
6.9.2.13.
Treatment Satisfaction Questionnaire for Medication
The TSQM is a composite measure based on the subject’s rating of medication effectiveness, 
side effects, and convenience. 
At Day 1, this questionnaire will be used to assess prior medications used to treat the subject’s 
CLE. At all other time points, the TSQM will be used to assess the subject’s opinion of the study 
drugs. Site staff should remind the subject of which CLE drugs they should be evaluating at each 
visit.
6.9.3.
Safety 
Safety will be assessed via AEs, concomitant medications, physical examinations (complete and 
symptom-driven), vital signs, ECGs, and clinical laboratory results.
6.9.4.
Clinical Laboratory Evaluations
The hematology, serum chemistry, and coagulation laboratory analyses will be performed at a 
central laboratory. Reference ranges will be supplied by the central laboratory and will be used 
by the investigator to assess the laboratory data for clinical significance and pathological 
changes.
Blood samples will be collected by venipuncture 
 
 in the arm at the time points indicated in the Study Procedures Table 
(Appendix 2). In addition, urine samples for the clinical laboratory assessments will be collected. 
An overnight fast (no food or drinks, except water) of at least 8 hours will be required prior to 
collection of blood samples for lipid testing.

Refer to Appendix 6 for table of clinical laboratory tests.
Laboratory values outside the normal range will be flagged and clinical relevance will be 
assessed by the investigator (refer to Section 7.5). More frequent sampling as well as additional 
tests may be performed as deemed necessary by the investigator. 
CCI


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Note that in the case where clinically significant laboratory test results are a potential reason for 
discontinuation from the study drug and/or withdrawal from the study, retesting of the affected 
parameter(s) should be prompt (within 3 to 7 days) (see Section 3.5 for additional information).
The details of sample handling and shipment instructions will be provided in a separate 
laboratory manual.  
6.9.5.
Vital Signs
Vital signs will be measured at the time points indicated in the Study Procedures Table 
(Appendix 2). 
Vital signs should be taken after the subject has been resting in the seated or supine position for 
at least 5 minutes and will include pulse rate, respiratory rate, systolic and diastolic blood 
pressure, and temperature.
6.9.6.
Physical Examination
A physical examination should be performed at the time points indicated in the Study Procedures 
Table (Appendix 2). Any changes from screening will be recorded. Weight will be measured at 
all visits. Height will be measured at screening only. Subjects should be instructed to remove 
shoes prior to measurement of height.
At screening, a complete physical examination will be performed. A complete physical 
examination will include source documentation of general appearance and the following body 
systems: head, neck, and thyroid; eyes, ears, nose, throat, mouth and tongue; chest 
(excluding breasts); respiratory; cardiovascular; lymph nodes; abdomen; skin, hair, nails; 
musculoskeletal; and neurological. Symptom-driven physical examinations will be performed at 
all other visits based on reported signs and symptoms.
6.9.7.
Other Safety Assessments
6.9.7.1.
12-lead Electrocardiogram
A resting 12-lead ECG will be performed at the time points indicated in the Study Procedures 
Table (Appendix 2).
The ECG should be obtained after the subject has been resting in the supine position for at least 
5 minutes and will include heart rate (HR), inter-beat (RR), QRS, uncorrected QT, morphology, 
and rhythm analysis. QT interval corrected for HR according to Fridericia (QTcF) will be 
derived during the statistical analysis. Electrocardiograms will be interpreted by the investigator 
(or qualified designee) for clinical significance and results will be entered into the eCRF.
6.10.
Pharmacokinetics Assessments
Blood samples for PK analysis will be collected at Week 2 (at least 30 minutes and up to 3 hours 
postdose), anytime at Week 4, and within 2 hours prior to study drug administration at Weeks 12 
and 24.  
Plasma concentrations of filgotinib, its metabolite (GS-829845), and GS-9876 will be analyzed.


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6.11.
Biomarker Assessments
Blood samples will be collected at screening, predose on Day 1 and at Weeks 2, 4, 12, 24, 48 
(for subjects entering the 24-week extension period), FU, and ET (if applicable).  
Blood samples may be analyzed for assessment of markers of inflammation, immune status, and 
JAK-STAT and SYK pathway activation.
 
 
 
 
 
 
6.12.
Photography 
Photography of areas of skin involvement should be performed at the time points indicated in the 
Study Procedures Table (Appendix 2).  Photographs may be used in exploratory analyses to 
evaluate association of images with other measures of CLE activity, such as CLASI data.
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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the
treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. AEs may also include pre- or post-treatment complications that occur as a 
result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. Preexisting events that increase in severity or change in nature during or 
as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion.
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (see Section 7.7.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
eCRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization


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


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


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7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead DSPH as instructed. This also includes any SAEs resulting from 
protocol-associated procedures performed after informed consent is signed.
Any SAEs and deaths that occur after the post-treatment follow-up visit but within 30 days of the 
last dose of study drug, regardless of causality, should also be reported. 
Investigators are not obligated to actively seek SAEs after the protocol defined follow up period. 
However, if the investigator learns of any SAEs that occur after study participation has 
concluded and the event is deemed relevant to the use of study drug, he/she should promptly 
document and report the event to Gilead DSPH.
Electronic Serious Adverse Event (eSAE) Reporting Process

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline. 

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead DSPH within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically, ie, the eCRF 
database is not functioning, record the SAE on the paper serious adverse event reporting 
form and submit within 24 hours to:
Gilead DSPH:
Fax:
E-mail:

As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF Database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary.

For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE form.
PPD
PPD


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7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
SUSARs. In accordance with the EU Clinical Trials Directive (2001/20/EC), Gilead or a 
specified designee will notify worldwide regulatory agencies and the relevant IEC in concerned 
Member States of applicable SUSARs as outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the IBs. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study investigational medicinal product (IMP). The investigator should notify the IRB 
or IEC of SUSAR reports as soon as is practical, where this is required by local regulatory 
agencies, and in accordance with the local institutional policy. 
To minimize the possibility of exposing study subjects to unusual risk, the safety information 
from this study will also be reviewed periodically by an independent Data Monitoring 
Committee (DMC; as described in Section 8.10). The DMC may have access to partially blinded 
or unblinded data and will make recommendations regarding the study according to the DMC 
charter
7.5.
Clinical Laboratory Abnormalities 
Asymptomatic laboratory abnormalities are usually not recorded as AEs or SAEs. However, 
laboratory abnormalities (eg, clinical chemistry, hematology, or urinalysis) that require medical 
or surgical intervention or lead to study drug interruption or discontinuation must be recorded as 
an AE or SAE, as applicable. In addition, laboratory or other abnormal assessments (eg, ECG, 
X-rays, vital signs) that are associated with signs and/or symptoms must be recorded as an AE or 
SAE if they meet the definition of an AE (or SAE) as described in Sections 7.1.1 and 7.1.2. If the 
laboratory abnormality is part of a syndrome, record the syndrome or diagnosis (ie, anemia) not 
the laboratory result (ie, decreased hemoglobin).
Severity should be recorded and graded according to the CTCAE (Appendix 4). For AEs 
associated with laboratory abnormalities, the event should be graded on the basis of the clinical 
severity in the context of the underlying conditions; this may or may not be in agreement with 
the grading of the laboratory abnormality.
7.6.
Toxicity Management 
All clinical toxicities and clinically significant laboratory toxicities will be managed according to 
the following uniform guidelines, which are detailed in Appendix 3.
For study-specific interruption and discontinuation criteria, refer to Section 3.5. The specific 
toxicity discontinuation criteria in Section 3.5 supercede the general toxicity guidelines. In 
general, if discrepancy is present, the more conservative criteria apply.


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The Gilead Medical Monitor should be consulted prior to study drug discontinuation ifmedically 
feasible.
7.6.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
For Grades 1 and 2 laboratory abnormalities or clinical events not specified in Section 3.5, 
continue study drug at the discretion of the investigator. 
7.6.2.
Grade 3 Laboratory Abnormality or Clinical Event
For Grade 3 laboratory abnormalities or clinical events not specified in Section 3.5, the following 
toxicity management guidelines apply:

For Grade 3 clinical event, or clinically significant (confirmed) laboratory abnormality, study 
drug may be continued if the event is considered to be unrelated to study drug. 

For a Grade 3 clinical event, or clinically significant (confirmed) laboratory abnormality, 
considered to be related to study drug, study drug should be interrupted until the toxicity 
returns to ≤Grade 2. 

If a laboratory abnormality recurs to ≥Grade 3 following re-challenge with study drug and is 
considered related to study drug, then study drug should be permanently discontinued and the 
subject managed according to local clinical practice. Recurrence of laboratory abnormalities 
considered unrelated to study drug may not require permanent discontinuation, and study 
drug may be continued at the discretion of the investigator. 
7.6.3.
Grade 4 Laboratory Abnormality or Clinical Event
For Grade 4 laboratory abnormalities or clinical events not specified in Section 3.5, the following 
toxicity management guidelines apply:

For a Grade 4 clinical event, or clinically significant (confirmed) laboratory abnormality, 
study drug should be permanently discontinued and the subject managed according to local 
clinical practice. The subject should be followed as clinically indicated until the laboratory 
abnormality returns to baseline or is otherwise explained, whichever occurs first. A clinically 
significant Grade 4 laboratory abnormality that is not confirmed by repeat testing should be
managed according to the algorithm for the new toxicity grade. 

Study drug may be continued without dose interruption for a clinically non-significant 
Grade 4 laboratory abnormality (eg, Grade 4 creatine kinase after strenuous exercise or 
nonfasting triglyceride elevation that can be medically managed) or a clinical event 
considered unrelated to the study drug(s). 
Grade 4 treatment-emergent toxicities should be noted by the investigator and brought to the 
attention of the Gilead Sciences Medical Monitor, who will discuss with the investigator and 
determine the appropriate course of action. All subjects experiencing AEs, regardless of if the 
AEs are treatment-related, must be monitored periodically until symptoms subside, any 


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abnormal laboratory values have resolved or returned to baseline levels or they are considered 
irreversible, or until there is a satisfactory explanation for the changes observed.
Histologic hemorrhage and thrombosis have been observed in cynomolgus monkeys that
received GS-9876 at doses ≥ 20 mg/kg/day. The clinical relevance of these findings to humans is 
unknown; these adverse events have not been reported in clinical studies of GS-9876. Any 
treatment-emergent adverse event involving significant bleeding or thrombosis is to be reported 
to the investigator and brought to the attention of the Gilead Sciences medical monitor or 
designee, to discuss the appropriate course of action.
Any questions regarding toxicity management should be directed to the Gilead Sciences 
Medical Monitor.
7.7.
Special Situations Reports
7.7.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, pregnancy reports regardless of an 
associated AE, an AE in an infant following exposure from breastfeeding, and an occupational 
exposure with an AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Occupational exposure with an AE is defined as exposure to medicinal product as result of one's 
professional or non-professional occupation. 
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
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7.7.2.
Instructions for Reporting Special Situations
7.7.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study drug and throughout the study, including the post study drug follow-up period, 
to Gilead DSPH using the pregnancy report form within 24 hours of becoming aware of the 
pregnancy. 
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.1.1 and Section 7.1.2. Furthermore, any SAE occurring as an adverse pregnancy 
outcome post study must be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH using the pregnancy outcome report 
form. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead DSPH. Gilead DSPH contact information is as follows: 
Email:
 and Fax: 
 
Refer to Appendix 5 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.7.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead DSPH within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study drug and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
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Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective of this study is as follows:

To evaluate the efficacy of filgotinib and GS-9876 in female subjects with 
moderately-to-severely active CLE
The secondary objective of this study is as follows: 

To evaluate the safety and tolerability of filgotinib and GS-9876 in moderately-to-severely 
active CLE
The exploratory objectives of this study are as follows:
 
 
 
 
8.1.2.
Primary Endpoint
The primary endpoint is change from baseline in CLASI activity score from baseline to
Week 12. 
8.1.3.
Secondary Endpoints
The secondary endpoints of this study are:

Proportion of subjects at Week 12 with decrease of ≥ 5 points in CLASI activity score from 
baseline 

Proportion of subjects at Week 12 with no worsening in CLASI activity score from baseline 
(worsening defined as ≥ 3 point increase)
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
Proportion of subjects at Week 24 with decrease of ≥5 points in CLASI activity score from 
baseline 

Proportion of subjects at Week 24 with no worsening in CLASI activity score from baseline 
(worsening defined as ≥3 point increase)
8.1.4.
Exploratory Endpoints
 
 
 
 
 
 
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All Randomized
The all randomized analysis set includes all subjects who are randomized in the study. This is the 
primary analysis set for by subject listings.
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8.2.1.2.
Efficacy
The primary analysis set for efficacy analyses will be the Full Analysis Set (FAS), which 
includes all randomized subjects who received at least one dose of study drug. 
8.2.1.3.
Safety
The primary analysis set for safety analyses will be the Safety Analysis Set, which includes all 
subjects who received at least one dose of study drug.
8.2.1.4.
Pharmacokinetics
The primary analysis set for PK analyses will be the PK analysis set, which includes all subjects 
in the Safety Analysis Set who have at least 1 nonmissing concentration data for the analyte of 
interest.
8.2.1.5.
Biomarkers
The primary analysis set for biomarker analyses will be the Biomarker Analysis Set, which
includes all randomized subjects who received at least one dose of study drug and have at least 
one baseline measurement available for the specific parameter of interest.
8.3.
Data Handling Conventions
Pharmacokinetic concentration values and PK parameter values below the limit of quantitation 
(BLQ) will be presented as “BLQ” in the data listings. Below the limit of quantitation values that 
occur prior to the first dose will be treated as 0, BLQ values at all other time points will be 
treated as 1/2 of the lower limit of quantitation (LLOQ).
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed to the value of the lower or upper limit 
minus or plus one significant digit, respectively (eg, if the result of a continuous laboratory test is 
< 20, a value of 19 will be assigned; if the result of a continuous laboratory test is < 20.0, a value 
of 19.9 will be assigned).
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized by treatment arm using standard 
descriptive statistics including sample size, mean, standard deviation (SD), median, 1st quartile 
(Q1), 3rd quartile (Q3), minimum, and maximum for continuous variables and number and 
percentages of subjects for categorical variables.
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8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary endpoint is the change in CLASI activity score from baseline to Week 12. The 
primary analysis will consist of superiority test of filgotinib 200 mg versus placebo and GS-9876 
30 mg versus placebo, respectively. The primary endpoint will be analyzed using a mixed-effect 
repeated measures (MMRM) model. The model may include terms for baseline CLASI value, 
treatment, visit, and treatment-by-visit interaction. Subjects will be included as a random effect.
8.5.2.
Secondary and Exploratory Analyses
For categorical endpoints, Cochran-Mantel-Haenszel approach adjusting for the randomization 
stratification factors will be used. For continuous endpoints, a similar MMRM approach will be 
used to evaluate treatment effect on change from baseline (Day 1). 
The summary statistics will be provided by treatment arm. Differences across treatment arms
will be summarized and treatment comparisons may be performed. Details on efficacy analyses 
will be described in the statistical analysis plan (SAP). 
8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set.
Safety will be evaluated by assessment of clinical laboratory tests, physical examinations, vital 
signs measurements at various time points during the study, and by the documentation of AEs.
All safety data collected on or after the date that study drug was first dispensed up to the date of 
last dose of study plus 30 days will be summarized by treatment arm (according to the study drug
received).
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug data will be generated from the study drug
administration page of the eCRF. Exposure data will be summarized by treatment arm. 
Duration of exposure to study drug will be expressed as the number of weeks between the first 
and last dose of the study drug, inclusive, regardless of temporary interruptions in study drug 
administration and summarized by treatment arm. 
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
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Treatment-Emergent Adverse Events (TEAEs) are defined as one or both of the following:

Any AEs with an onset date of on or after the study drug start date and no later than 30 days 
after permanent discontinuation of study drug or

Any AEs leading to premature discontinuation of study drug.
Summaries (number and percentage of subjects) of TEAEs by SOC and PT will be provided by 
treatment arm. Treatment-emergent adverse events will also be summarized by relationship to 
study drug and severity. In addition, TEAEs leading to premature discontinuation of study drug 
will be summarized and listed.
8.6.3.
Laboratory Evaluations
Selected laboratory data will be summarized (n, mean, SD, median, Q1, Q3, minimum, and 
maximum) by treatment arm. Absolute values and change from baseline at all scheduled 
timepoints will be summarized.
Graded laboratory abnormalities will be defined using CTCAE 4.03 grading scale.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
one toxicity grade from baseline at any time post baseline up to the date of last dose of study 
drug plus 30 days, will be summarized by treatment.
8.6.4.
Other Safety Evaluations
Individual data for physical examination findings, prior and concomitant medications and 
medical history will be provided. 
8.7.
Pharmacokinetic Analysis
Plasma concentrations of filgotinib, its metabolite (GS-829845), and GS-9876 will be listed and 
summarized using descriptive statistics (eg, sample size, arithmetic mean, geometric mean, 
% coefficient of variation, standard deviation, median, minimum, and maximum). Plasma 
concentrations of each analyte over time may be plotted in semi logarithmic and linear formats 
as mean standard deviation.
8.8.
Biomarker Analysis
For analysis of the pharmacodynamics markers, the baseline level and the modulation pattern 
upon treatment, including change over time from baseline level, will be evaluated by treatment 
arm. Descriptive statistics will be provided at each sampling time, by treatment arm. 
Additionally graphical summaries, eg, mean ± SD, median ± interquartile range (Q1, Q3), box 
plots, and scatter plots to explore correlations between different biomarkers may also be 
generated, as needed. These graphs may be generated for raw values as well as change from 
baseline, as appropriate.
 
 
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8.9.
Sample Size
With a sample size of 50 subjects (20 in each active treatment arm and 10 in the placebo arm), 
there is a 79% power to detect a 2-point difference between each active arm and the placebo arm 
in the primary endpoint using a 2-sided 0.1-level test, assuming a common standard deviation of 
2 and a 10% drop-out rate per arm.
8.10.
Data Monitoring Committee
An external multidisciplinary DMC will review the progress of the study and perform interim 
reviews of safety data and provide recommendations to Gilead on whether the nature, frequency, 
and severity of adverse effects associated with study treatment warrant the early termination of 
the study in the best interests of the participants, whether the study should continue as planned, 
or whether the study should continue with modifications.
The first DMC meeting will be conducted after approximately 50% of the subjects have 
completed their Week 12 study visit. The DMC’s specific activities will be defined by a mutually 
agreed charter, which will define the DMC’s membership, conduct and meeting schedule.
While the DMC will be asked to advise Gilead regarding future conduct of the study, including 
possible early study termination, Gilead retains final decision-making authority on all aspects of 
the study.
8.11.
Analysis Schedule
The primary analysis will be conducted when all enrolled subjects either complete their Week 12
visit or prematurely discontinue from the study. The final analysis will be performed when all 
subjects complete the study or prematurely discontinue from the study.
Additionally, to assess the safety and efficacy of GS-9876 and filgotinib for further planning and 
development of these products, a Gilead internal unblinded team independent of the blinded 
study team will be assembled. This group will consist of at least one representative from Clinical 
Research, Biostatistics, and Pharmacovigilance/Epidemiology, and may include other personnel 
as necessary. The Gilead internal unblinded team will be granted access to unblinded clinical 
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data including treatment assignments to closely monitor study progress and drug safety. The 
membership, responsibilities, conduct, specific activities and meeting schedule of the unblinded 
internal team will be documented in a Gilead Internal Unblinded Team Charter.  
To mitigate the risks of inadvertently releasing the treatment information to the sites and 
subjects, the internal team will keep the unblinded information confidential and will not 
communicate the information to the blinded study team, site staff or subjects. Data unblinding 
due to medical emergency will follow standard Gilead procedures.


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


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and the person conducting the consent discussion, and also by an impartial witness if required by 
IRB/IEC local requirements.
 
9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form or biological sample submitted to the Sponsor, IRB/IEC, or laboratory. Laboratory 
specimens must be labeled in such a way as to protect subject identity while allowing the results 
to be recorded to the proper subject. Refer to specific laboratory instructions. NOTE: The 
investigator must keep a screening log showing codes, names, and addresses for all subjects 
screened and for all subjects enrolled in the trial. Subject data will be processed in accordance 
with all applicable regulations.
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, eCRF, the IMP, and any other study information, remain the 
sole and exclusive property of Gilead during the conduct of the study and thereafter. This 
information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, 
IRB/IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);

Documentation of the reason(s) a consented subject is not enrolled
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
Participation in study (including study number);

Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of IMP, including dates of dispensing and return;

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF casebook will be completed by an authorized study staff 
member whose training for this function is completed in EDC. The eCRF casebook will only 
capture the data required per the protocol schedule of events and procedures. The 
Inclusion/Exclusion Criteria and Enrollment eCRFs should be completed only after all data 
related to eligibility have been received. Subsequent to data entry, a study monitor will perform 
source data verification within the EDC system. System-generated or manual queries will be 
issued to the investigative site staff as data discrepancies are identified by the monitor or internal 


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


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


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


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10.
REFERENCES
Barr PM, Wei C, Roger J, Schaefer-Cutillo J, Kelly JL, Rosenberg AF, et al. Syk inhibition with 
fostamatinib leads to transitional B lymphocyte depletion. Clin Immunol 
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Braegelmann C, Holzel M, Ludbrook V, Dickson M, Turan N, Ferring-Schmitt S, et al. Spleen 
tyrosine kinase (SYK) is a potential target for the treatment of cutaneous lupus 
erythematosus patients. Experimental dermatology 2016;25 (5):375-9.
Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, et al. R406, an orally available 
spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune 
complex-mediated inflammation. J Pharmacol Exp Ther 2006;319 (3):998-1008.
Carneiro JR, Sato EI. Double blind, randomized, placebo controlled clinical trial of methotrexate 
in systemic lupus erythematosus. The Journal of rheumatology 1999;26 (6):1275-
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Chan ES, Herlitz LC, Jabbari A. Ruxolitinib Attenuates Cutaneous Lupus Development in a 
Mouse Lupus Model. J Invest Dermatol 2015;135 (7):1912-5.
Coffey G, DeGuzman F, Inagaki M, Pak Y, Delaney SM, Ives D, et al. Specific inhibition of 
spleen tyrosine kinase suppresses leukocyte immune function and inflammation in 
animal models of rheumatoid arthritis. J Pharmacol Exp Ther 2012;340 (2):350-9.
Deng GM, Liu L, Bahjat FR, Pine PR, Tsokos GC. Suppression of skin and kidney disease by 
inhibition of spleen tyrosine kinase in lupus-prone mice. Arthritis Rheum 2010;62 
(7):2086-92.
Gronhagen CM, Fored CM, Granath F, Nyberg F. Cutaneous lupus erythematosus and the 
association with systemic lupus erythematosus: a population-based cohort of 1088 
patients in Sweden. Br J Dermatol 2011;164 (6):1335-41.
Holm JG, Agner T, Clausen ML, Thomsen SF. Quality of life and disease severity in patients 
with atopic dermatitis. J Eur Acad Dermatol Venereol 2016.
Jarrett P, Thornley S, Scragg R. Ethnic differences in the epidemiology of cutaneous lupus 
erythematosus in New Zealand. Lupus 2016;25 (13):1497-502.
Klein RS, Morganroth PA, Werth VP. Cutaneous Lupus and the Cutaneous Lupus 
Erythematosus Disease Area and Severity Index (CLASI) Instrument. Rheumatic 
diseases clinics of North America 2010;36 (1):33-51, vii.
Namour F, Diderichsen PM, Cox E, Vayssiere B, Van der Aa A, Tasset C, et al. 
Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib 
(GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection. 
Clin Pharmacokinet 2015;54 (8):859-74.


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FINAL
Gilead Sciences, Inc. 
Amendment 4
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Ruzicka T, Sommerburg C, Goerz G, Kind P, Mensing H. Treatment of cutaneous lupus 
erythematosus with acitretin and hydroxychloroquine. Br J Dermatol 1992;127 
(5):513-8.
Schmitt J, Rosumeck S, Thomaschewski G, Sporbeck B, Haufe E, Nast A. Efficacy and safety of 
systemic treatments for moderate-to-severe psoriasis: meta-analysis of 
randomized controlled trials. Br J Dermatol 2014;170 (2):274-303.
Vital EM, Wittmann M, Edward S, Md Yusof MY, MacIver H, Pease CT, et al. Brief report: 
responses to rituximab suggest B cell-independent inflammation in cutaneous 
systemic lupus erythematosus. Arthritis Rheumatol 2015;67 (6):1586-91.
Wieczorek IT, Propert KJ, Okawa J, Werth VP. Systemic symptoms in the progression of 
cutaneous to systemic lupus erythematosus. JAMA dermatology 2014;150 
(3):291-6.
Winkelmann RR, Kim GK, Del Rosso JQ. Treatment of Cutaneous Lupus Erythematosus: 
Review and Assessment of Treatment Benefits Based on Oxford Centre for 
Evidence-based Medicine Criteria. J Clin Aesthet Dermatol 2013;6 (1):27-38.
Wouters CH, Diegenant C, Ceuppens JL, Degreef H, Stevens EA. The circulating lymphocyte 
profiles in patients with discoid lupus erythematosus and systemic lupus 
erythematosus suggest a pathogenetic relationship. Br J Dermatol 2004;150 
(4):693-700.


GS-9876
Protocol GS-US-436-4092
FINAL
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 86
15 October 2018
11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table
Appendix 3.
Management of Clinical and Laboratory Adverse Events
Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Appendix 5.
Pregnancy Precautions, Definitions of Females of Childbearing Potential, and 
Contraceptive Requirements
Appendix 6.
Clinical Laboratory Assessment Table
Appendix 7.
Physician’s Global Assessment of CLE Disease Activity
Appendix 8.
Subject Global Assessment of CLE Disease Activity and Other Subject Reported 
Measures


PPD
PPD
GS-9876 
Protocol GS-US-436-4092 
FINAL 
Gilead Sciences, Inc. 
Amendment 4 
Appendix 1. 
lnvestigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 2, Randomized, Doub]e-Blind, Placebo-Controlled Study to Assess the Safety and 
Efficacy of Filgotinib and GS-9876 in Female Subjects with Moderately-To-Severely Active 
Cutaneous Lupus Erythematosus (CLE) 
GS-US-436-4092, Amendment 4, 15 October 2018 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
Name (Printed) 
Author 
Date 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully infonned about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 87 
15 October 20 I 8 


GS-9876
Protocol GS-US-436-4092
FINAL
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 88
15 October 2018
Appendix 2.
Study Procedures Table
Study Procedures
Screena
Study Dosing Period
24-week Extension Period
ETc
F/Ud
Day 1b
Week 
2
Week 
4
Week 
8
Week 
12
Week 
14
Week 
16
Week 
20
Week 
24
Week 
30
Week 
36
Week 
42
Week 
48
± 2 
days
± 3 
days
± 3 
days
± 3 
days
± 5 
days
± 5 
days
± 5 
days
± 5 
days
± 7 
days
± 7 
days
± 7 
days
± 7 
days
± 5 
days
± 5 
days
Written Informed Consent
X
Review of Inclusion/ 
Exclusion Criteria
X
Medical Historye
X
X
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Complete Physical 
Examination
X
Symptom-driven Physical 
Examinationf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signsg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physician’s Global 
Assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CLASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Detailed Target Lesion 
Assessmentv
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Photography of Areas with 
Skin Involvementw
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Detailed Mucous 
Membrane Assessmentx
X
X
X
X
X
X
X
Subject’s Global 
Assessment and other 
subject-reported measuresh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xi


GS-9876
Protocol GS-US-436-4092
FINAL
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 89
15 October 2018
Study Procedures
Screena
Study Dosing Period
24-week Extension Period
ETc
F/Ud
Day 1b
Week 
2
Week 
4
Week 
8
Week 
12
Week 
14
Week 
16
Week 
20
Week 
24
Week 
30
Week 
36
Week 
42
Week 
48
± 2 
days
± 3 
days
± 3 
days
± 3 
days
± 5 
days
± 5 
days
± 5 
days
± 5 
days
± 7 
days
± 7 
days
± 7 
days
± 7 
days
± 5 
days
± 5 
days
12-lead ECG
X
X
X
X
Xy
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fasting Lipidsj
X
X
X
X
CRP and ESR
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HbA1c and TSH
X
Urinalysis and Urine 
protein to creatinine 
ratio
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Drug and Alcohol 
Screen
X
Serum Pregnancy Testk
X
Urine Pregnancy Testk, l
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
FSH Testm
X
HIV-1, HIV-2, HBV, HCV
Serology
X
HCV Monitoringn
X
X
X
X
Xy
Quantiferon Testo
X
Chest X-rayo
X
Quantitative Serum 
Immunoglobulin Test
X
X
X
X
Autoantibody Panel
X
X
X
X


GS-9876
Protocol GS-US-436-4092
FINAL
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 90
15 October 2018
Study Procedures
Screena
Study Dosing Period
24-week Extension Period
ETc
F/Ud
Day 1b
Week 
2
Week 
4
Week 
8
Week 
12
Week 
14
Week 
16
Week 
20
Week 
24
Week 
30
Week 
36
Week 
42
Week 
48
± 2 
days
± 3 
days
± 3 
days
± 3 
days
± 5 
days
± 5 
days
± 5 
days
± 5 
days
± 7 
days
± 7 
days
± 7 
days
± 7 
days
± 5 
days
± 5 
days
Complement Levels
X
X
X
X
X
X
Pharmacokineticsp
X
X
X
X
Whole Blood, Cytochex
X
Xs
X
X
X
X
X
Whole Blood, Heparin
X
Xs
X
X
X
X
X
Serum biomarker sample
X
Xs
X
X
X
X
X
X
X
Plasma biomarker sample
X
Xs
X
X
X
X
X
X
X
vfPBMC
X
Xs
X
X
X
X
X
PAXgene RNA sample
X
Xs
X
X
X
X
X
X
X
Randomization
X
Xt
Study Drug Dispensing
X
X
X
X
X
X
Xu
X
X
X
Study Drug Accountability
X
X
X
X
X
X
X
X
X
X
X
X
X
Review AEs & 
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Prospective subjects should be screened no more than 28 days prior to randomization and administration of the first dose of study drugs.
b
Day 1 procedures, including study drug administration, will be performed at the study center. All assessments will be performed prior to dosing unless otherwise indicated.
c
Subjects who discontinue from the study prior to Week 24 (or prior to Week 48 for subjects entering the 24-week extension period), will return to the study center for ET 
assessments.
d
Subjects will return to the study center for a FU visit 4 weeks (± 5 days) after their last dose of study drug. Subjects who discontinue study drug ≥4 weeks prior to their 
last visit will not be asked to return for the FU visit.
e
At screening, medical history will include collection of demographics and a review of surgical history and CLE history (including documentation of prior skin biopsy results, 
if available). Medical history will be updated, as needed, on Day 1.
f
Symptom-driven physical examinations will be performed, as needed, based on signs and symptoms.
g
Vital signs include resting blood pressure, heart rate, respiratory rate, and temperature. 
CCI
-----------------------------------------------------------------------------


GS-9876
Protocol GS-US-436-4092
FINAL
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 91
15 October 2018
h
Includes VAS (subject assessment of CLE on sexual activity; autoimmune disease-related dry eyes/mouth, body pain, joint pain/stiffness, and fatigue), SF-36, DLQI, and 
TSQM. Subject reported outcomes are recommended to be performed at the beginning of each visit prior to any other visit-related procedures (other than signing of informed 
consent). 
i
The TSQM will not be administered at the FU visit.
j
An overnight fast (no food or drinks, except water) of at least 8 hours is required prior to collection of blood samples for lipid testing.
k
Females of childbearing potential only (see Appendix 5). 
l
When visits are greater than 4 weeks apart, women should continue to have urine pregnancy tests every 4 weeks using at home pregnancy test kits that will be provided to 
them. The site will call the subject every 4 weeks to obtain results of these pregnancy tests and will record the information in the source documents and eCRF. If any urine 
pregnancy test is positive, study drug should be immediately interrupted and the subject should return to the study center for a serum pregnancy test.
m
Females of non-childbearing potential only (see Appendix 5).
n
Viral monitoring for HCV every 12 weeks, as applicable (see exclusion criteria, Section 4.3).
o
Subjects previously treated for latent TB (see Inclusion # 9) do not need to have the QuantiFERON® TB-Gold In-Tube test (or equivalent assay), but a chest radiograph must 
be obtained if one is not available within 3 months prior to screening (with the report or films available for investigator review). All other subjects must have the 
QuantiFERON® TB-Gold In-Tube test (or equivalent assay) at screening and a chest radiograph (views as per local guidelines) at screening or within 3 months prior to
screening (with the report or films available for investigator review).
p
Pharmacokinetic samples will be collected on Week 2 (at least 30 minutes and up to 3 hours after dosing), Week 4 (anytime), Week 12 (within 2 hours prior to study drug 
administration), and Week 24 (within 2 hours prior to study drug administration).
 
s
On Day 1, biomarker samples will be collected prior to study drug administration.
t
At the end of the Week 12 visit, subjects on placebo will be re-randomized 1:1 in a blinded fashion to receive filgotinib 200 mg + PTM GS-9876 30 mg once daily or 
GS-9876 30 mg + PTM filgotinib 200 mg once daily for the remainder of the study.
u
For subjects who enter the 24-week extension period only.
v
See Section 6.9.2.3 for details.
w
A separate manual will be provided for instructions on photography of areas with skin involvement.
x
See Section 6.9.2.4 for details.
y
To be performed at ET visit if not completed within the prior 12 weeks.
CCI
CCI' 


GS-9876
Protocol GS-US-436-4092
FINAL
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 92
15 October 2018
Appendix 3.
Management of Clinical and Laboratory Adverse Events
*
Refer to Sections 3.5 and 7.5 for details
Gradel 
.______
Gra
- de-2 ____.I 
J.______
Grad
_
e_3 ____.I ~I --G- ra-de 4 _ 
____. 
! 
May continue 
Repeat lab to 
dosing at tlte 
confirm toxicity 
discretion of tlte 
grade 
investigator 
If confirmed and possibly and/orprobably related to 
investigational medicinal products: 
I. WiihhoW investigational medicinal products wttil 
Grade 2 
2. Restart all inve~ational medicinal products at full dose 
l 
If Grade 3 or 4 n :cui-rence that is confirmed and possibly or 
probably related to imrestigational medicinal products, 
discontinue all investigational medicinal products dosing 
permanently 
Repeat lab to 
confirm toxicity 
gi"ade 
, 
l 
If confirmed and umselated to 
investigational medicinal 
products, dosing may continue at 
tlte discretion oftlte investigator 
--+ 
Ifconfirmed and 
possibly or prob ably 
related to 
inv estiga tio nal 
medicinal products, 
discontinue 
inv estiga tio nal 
medicinal products 
dosingpennanently 
and follow at 
periodic inteivak at 
least weekly wttil a 
return to baseline or 
is o tltenv isie 
expb.ined 
If Grade 3 or 4 recui-rence tlta t is considered unrelated to 
investigational medicinal products, continue all 
investigational medicinal products at tlte same dose at tlte 
discretion of tlte investigator 


GS-9876
Protocol GS-US-436-4092
FINAL
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 93
15 October 2018
Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Please refer to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03, 
which can be found at:
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf 
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
The only modification to the CTCAE criteria is the addition of a Grade 1 upper respiratory 
infection as follows:
CTCAE 
v4.0 Term
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
CTCAE v4.03 AE 
Term Definition
Upper 
respiratory 
infection
Mild symptoms; 
symptomatic 
relief (eg, cough 
suppressant, 
decongestant)
Moderate 
symptoms; oral 
intervention 
indicated 
(eg, antibiotic, 
antifungal, 
antiviral)
IV antibiotic, 
antifungal, or 
antiviral 
intervention 
indicated; 
radiologic, 
endoscopic, or 
operative 
intervention 
indicated
Life-threatening 
consequences; 
urgent 
intervention 
indicated
Death
A disorder 
characterized by an 
infectious process 
involving the upper 
respiratory tract 
(nose, paranasal 
sinuses, pharynx, 
larynx, or trachea).


GS-9876
Protocol GS-US-436-4092
FINAL
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 94
15 October 2018
Appendix 5.
Pregnancy Precautions, Definitions of Females of Childbearing 
Potential, and Contraceptive Requirements
The administration of filgotinib in embryo-fetal animal development studies resulted in 
decreased numbers of viable rat fetuses, increased resorptions, and visceral and skeletal 
malformations. Similar effects were noted in the rabbit. A safety margin relative to human 
exposure has not been identified. Therefore, filgotinib is contraindicated during pregnancy.
Non-clinical reproductive toxicity studies of GS-9876 do not indicate a strong suspicion of 
human teratogenicity/fetotoxicity.  There are no data for GS-9876 in pregnant women.
For participation in this study, the use of highly effective contraception is required as outlined 
below for all subjects of childbearing potential. In addition, women of childbearing potential 
should have a urine pregnancy test every 4 weeks during the study.
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, 
permanently sterile or with medically documented ovarian failure. Women who do not meet the 
protocol definitions of post-menopausal, or permanently sterile, or do not have medically 
documented ovarian failure, must have pregnancy testing as outlined in the protocol. 
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women < 54 years of age with amenorrhea of > 12 months may also be considered 
postmenopausal if their FSH level is in the postmenopausal range and they are not using 
hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age. Bilateral tubal ligation is not considered to be 
permanent sterilization.
2) Contraception for Female Subjects
a. Study Drug Effects on Pregnancy and Hormonal Contraception
Filgotinib is contraindicated in pregnancy as there is a possibility of human 
teratogenicity/fetotoxicity in early pregnancy based on non-clinical data. Data from a clinical 
drug-drug interaction study of filgotinib and hormonal contraceptives demonstrated that 
filgotinib does not alter the pharmacokinetics of representative hormonal contraceptives
levonorgestrel/ethinyl estradiol.
GS-9876 has not been studied in pregnant women. There is no evidence of human teratogenicity 
based on class effects or genotoxic potential. In vitro drug interaction assessment of GS-9876 
and hormonal contraceptives suggests that there is no clinically relevant effects that would 
decrease contraceptive efficacy.
Please refer to the latest version of the IBs for filgotinib and GS-9876 for additional information.


GS-9876
Protocol GS-US-436-4092
FINAL
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 95
15 October 2018
b. Contraception for Female Subjects of Childbearing Potential
Women of childbearing potential must have a negative serum pregnancy test at screening and a 
negative urine pregnancy test at the Day 1 visit prior to randomization. Pregnancy tests will be 
performed at monthly intervals thereafter. In the event of a delayed menstrual period 
(> one month between menstruations), a pregnancy test must be performed to rule out pregnancy. 
This is true even for women with infrequent or irregular periods. 
Female subjects of childbearing potential must agree to use highly effective contraception. 
Subjects must agree to use one of the following methods from screening until 36 days following 
the last dose of study drug. 

Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual 
lifestyle.
Or

Consistent and correct use of 1 of the following methods of birth control listed below:
Intrauterine device (IUD) with a failure rate of < 1% per year
Tubal sterilization
Essure micro-insert system (provided confirmation of success 3 months after procedure)
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)

Female subjects who wish to use a hormonal contraceptive must agree to use it in 
conjunction with a barrier method, preferably a male condom.  Female subjects who utilize a 
hormonal contraceptive as one of their birth control methods must have consistently used the 
same method for at least three months prior to study drug dosing.  Hormonal contraceptives 
and barrier methods permitted for use in this protocol are as follows:
Barrier methods (each method must be used with a hormonal method):
■
Male condom (with or without spermicide)
■
Female condom (with or without spermicide)
■
Diaphragm with spermicide
■
Cervical cap with spermicide
■
Sponge with spermicide


GS-9876
Protocol GS-US-436-4092
FINAL
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 96
15 October 2018
Hormonal methods (each method must be used with a barrier method, preferably a male 
condom):
■
Oral contraceptives (either combined or progesterone only)
■
Injectable progesterone
■
Subdermal contraceptive implant
■
Transdermal contraceptive patch
■
Contraceptive vaginal ring
All female subjects must also agree to refrain from egg donation and in vitro fertilization during 
the study and until 36 days after the last study drug dose.
3) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method (LAM). Female condom and male condom should not be used 
together.
4) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 36 days of last study drug dose. Subjects who 
become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator and discontinue all study drugs immediately. 
Instructions for reporting pregnancy, and pregnancy outcome are outlined in Section 7.7.2.1.
5) Pregnancy Testing
All females of childbearing potential will have urine pregnancy testing every 4 weeks during the
study. During the periods where study visits are every 6-8 weeks, women should continue to 
have pregnancy tests every 4 weeks, using home pregnancy test kits that will be provided to 
them. The site will call the subject every 4 weeks to obtain the results of these pregnancy tests 
and will record the information in the source documents and eCRF. If a positive urine pregnancy 
test is reported, the female subject will be asked to stop all study drugs and return to the clinic for
a serum pregnancy test.


GS-9876
Protocol GS-US-436-4092
FINAL
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 97
15 October 2018
Appendix 6.
Clinical Laboratory Assessment Table
Hematology
Chemistry
Urinalysis
Other
White blood cell (WBC) 
count
Hematocrit
Hemoglobin
Red blood cell (RBC) 
count
Red blood cell indices
Platelet count
Differentials (absolute 
and percentage), 
including, but not 
limited to:
Lymphocytes
Monocytes
Neutrophils
Eosinophils
Basophils
Reticulocyte count
Alkaline phosphatase
Aspartate 
aminotransferase (AST)
Alanine aminotransferase 
(ALT)
Gamma-glutamyl 
transpeptidase (GGT)
Total bilirubin
Direct and indirect 
bilirubin
Total protein
Albumin
Bicarbonate
Blood urea nitrogen 
(BUN)
Calcium
Chloride
Creatinine
Creatinine clearance,
CLcr*
Glucose
Phosphorus
Magnesium
Potassium
Sodium
Creatine Kinase (CK)
Amylase
Lipase
Uric acid (at screening 
only)
Appearance
Blood
Color
Glucose
Specific gravity
Nitrites
Leukocyte esterase
pH
Protein
Ketones
Bilirubin
Urobilinogen
Reflex to microscopic 
urinalysis if dipstick result 
is abnormal.
Urine protein to creatinine 
ratio
Urine drug screen for:
Amphetamines
Cocaine
Barbiturates
Opiates
Benzodiazepines
QuantiFERON® TB – Gold 
In-Tube Analysis (if required 
per inclusion criteria)
FSH (as applicable)
HbA1c (at screening only)
TSH (at screening only)
C-reactive protein (CRP)
Erythrocyte sedimentation rate 
(ESR)
Quantitative immunoglobulins 
(IgG, IgM, and IgA)
Autoantibody panel (ANA with 
reflex ENA (dsDNA, SSA, 
SSB, Smith, RNP))
Complement levels (C3, C4, 
and CH50)
Virology
Hepatitis B surface antigen 
(HBsAg)
Hepatitis B virus (HBV)
core antibody
Hepatitis C Virus (HCV)
Ab (if positive, then reflex 
HCV RNA)
Human immunodeficiency 
virus Ab
Coagulation
Fasting Lipids
Pregnancy
Activated partial 
thromboplastin time 
(aPTT)
Prothrombin time (PT)
International normalized 
ratio (INR)
Total cholesterol
Low-density lipoprotein 
(LDL)
High-density lipoprotein 
(HDL)
Triglycerides
In females of childbearing 
potential:
Serum pregnancy test
Urine pregnancy test
*
Calculation based on actual body weight,
Females: 0.85×(140−Age[years])×Weight[kg]/(Creatinine[mg/dL]×72)
ANA = antinuclear antibody
ENA = extractable nuclear antigen
dsDNA = double stranded DNA
Sm = Smith antigen
P protein = phosphorylated protein
SSA = Sjogren’s-syndrome-related antigen A
SSB = Sjogren’s-syndrome-related antigen B


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Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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Appendix 7.
Physician’s Global Assessment of CLE Disease Activity
A horizontal visual analog scale will be used to record the physician’s assessment of the patient’s 
CLE disease activity.
Instructions: 
Place a mark on the line below to indicate the subject’s current CLE disease activity 
(independent of the subject’s self-assessment):
No CLE disease activity                                                                                 Maximum CLE disease activity


GS-9876 
Protocol GS-US-436-4092 
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Gilead Sciences, Inc.  
Amendment 4 
CONFIDENTIAL 
Page 99 
15 October 2018 
Appendix 8. 
Subject Global Assessment of CLE Disease Activity and Other 
Subject Reported Measures 
1. 
Subject Global Assessment of CLE Disease Activity 
A horizontal, visual analog scale will be used to provide the subject’s overall assessment of CLE 
disease activity. 
Instructions: 
Place a mark on the line below to indicate how active your skin condition (CLE) has been 
over the last week: 
 
I have no CLE  
 
                                 
 
 
I have the worst CLE 
2. 
Subject Assessment of Autoimmune Disease-related Dry Eyes/Mouth 
A horizontal, visual analog scale will be used to provide the subject’s overall assessment of 
autoimmune disease-related dry eyes. 
Place a mark on the line below to indicate how much dry eye has been caused by your 
autoimmune condition over the last week: 
 
 
A horizontal, visual analog scale will be used to provide the subject’s overall assessment of 
autoimmune disease-related dry mouth. 
Place a mark on the line below to indicate how much dry mouth has been caused by your 
autoimmune condition over the last week: 
 
 
 
 
 
 
 
3. 
Subject Assessment of Autoimmune Disease-related Body Pain 
A horizontal, visual analog scale will be used to provide the subject’s overall assessment of 
autoimmune disease-related body pain. 
I have no dry mouth due to my 
autoimmune condition 
I have the worst dry mouth due 
to my autoimmune condition 
I have no dry eye due to my 
autoimmune condition 
I have the worst dry eye due to 
my autoimmune condition 


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Amendment 4
CONFIDENTIAL
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Place a mark on the line below to indicate how much body pain has been caused by your 
autoimmune condition over the last week:
4.
Subject Assessment of Autoimmune Disease-related Joint Pain/Stiffness
A horizontal, visual analog scale will be used to provide the subject’s overall assessment of 
autoimmune disease-related joint pain.
Place a mark on the line below to indicate how much joint pain has been caused by your
autoimmune condition over the last week:
A horizontal, visual analog scale will be used to provide the subject’s overall assessment of 
autoimmune disease-related joint stiffness.
Place a mark on the line below to indicate how much joint stiffness has been caused by
your autoimmune condition over the last week:
I have no body pain due to my 
autoimmune condition
I have the worst body pain due 
to my autoimmune condition
I have no joint paint due to my 
autoimmune condition
I have the worst joint pain due to 
my autoimmune condition
I have no joint stiffness due to 
my autoimmune condition
I have the worst joint stiffness 
due to my autoimmune condition


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5.
Subject Assessment of Autoimmune Disease-related Fatigue
A horizontal, visual analog scale will be used to provide the subject’s overall assessment of 
autoimmune disease-related fatigue.
Place a mark on the line below to indicate how much fatigue has been caused by your 
autoimmune condition over the last week:
6.
Subject Assessment of CLE on Sexual Activity
A horizontal, visual analog scale will be used to provide the subject’s overall assessment of CLE 
on sexual activity.
Place a mark on the line below to indicate how much your sexual activity has been affected 
by your skin condition (CLE) over the last week:
My CLE does not affect my sexual activity
My CLE completely stops my sexual activity
I have no fatigue due to my 
autoimmune condition
I have the worst fatigue due to 
my autoimmune condition

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 2, Randomized, Double-blind, Placebo-controlled Study 
to Assess the Safety and Efficacy of Filgotinib and GS-9876 in 
Female Subjects with Moderately-to-Severely Active Cutaneous 
Lupus Erythematosus (CLE)
Name of Test Drug:
Filgotinib and Lanraplenib (GS-9876)
Study Number:
GS-US-436-4092
Protocol Version (Date):
Amendment 4 (15 October 2018)
Analysis Type:
Final
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
13 May 2019
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(r) GILEAU 


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TABLE OF CONTENTS
LIST OF ABBREVIATIONS........................................................................................................................................4
PHARMACOKINETIC ABBREVIATIONS................................................................................................................6
1.
INTRODUCTION ................................................................................................................................................7
1.1.
Study Objectives ......................................................................................................................................7
1.2.
Study Design............................................................................................................................................7
1.3.
Sample Size and Power............................................................................................................................9
2.
TYPE OF PLANNED ANALYSES ...................................................................................................................10
2.1.
Interim Analyses ....................................................................................................................................10
2.1.1.
External Safety DMC...........................................................................................................10
2.1.2.
Internal Data Monitoring......................................................................................................10
2.2.
Primary (Week 12) Analysis..................................................................................................................10
2.3.
Final Analysis ........................................................................................................................................11
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................12
3.1.
Analysis Sets..........................................................................................................................................12
3.1.1.
All Randomized Analysis Set...............................................................................................12
3.1.2.
Full Analysis Set ..................................................................................................................12
3.1.3.
Safety Analysis Set...............................................................................................................12
3.1.4.
Per-Protocol Analysis Set.....................................................................................................12
3.1.5.
Pharmacokinetic Analysis Set..............................................................................................13
3.1.6.
Biomarker Analysis Set........................................................................................................13
3.2.
Subject Grouping ...................................................................................................................................13
3.3.
Strata and Covariates..............................................................................................................................14
3.4.
Examination of Subject Subgroups........................................................................................................14
3.5.
Multiple Comparisons............................................................................................................................14
3.6.
Missing Data and Outliers......................................................................................................................15
3.6.1.
Missing Data ........................................................................................................................15
3.6.2.
Outliers.................................................................................................................................15
3.7.
Data Handling Conventions and Transformations .................................................................................15
3.8.
Analysis Visit Windows.........................................................................................................................16
3.8.1.
Definition of Study Day .......................................................................................................16
3.8.2.
Analysis Visit Windows.......................................................................................................16
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit.............................18
3.9.
Efficacy Estimands.................................................................................................................................19
4.
SUBJECT DISPOSITION ..................................................................................................................................20
4.1.
Subject Enrollment and Disposition.......................................................................................................20
4.2.
Extent of Study Drug Exposure and Adherence.....................................................................................21
4.2.1.
Duration of Exposure to Study Drug....................................................................................21
4.2.2.
Adherence to Study Drug.....................................................................................................22
4.3.
Protocol Deviations................................................................................................................................23
5.
BASELINE CHARACTERISTICS....................................................................................................................24
5.1.
Demographics ........................................................................................................................................24
5.2.
Baseline Characteristics .........................................................................................................................24
5.3.
Medical History......................................................................................................................................25
6.
EFFICACY ANALYSES ...................................................................................................................................26
6.1.
Definition of the Primary Efficacy Endpoints........................................................................................26
6.2.
Analysis of the Primary Efficacy Endpoint............................................................................................26


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6.3.
Sensitivity Analysis of Primary Endpoint..............................................................................................27
6.4.
Secondary Efficacy Endpoints ...............................................................................................................27
6.4.1.
Definition of Secondary Efficacy Endpoints........................................................................27
6.4.2.
Analysis Methods for Secondary Efficacy Endpoint............................................................28
6.5.
Exploratory Efficacy Endpoints.............................................................................................................28
6.5.1.
Definition of Exploratory Efficacy Endpoints......................................................................28
6.5.2.
Analysis Methods for Exploratory Efficacy Endpoints........................................................29
6.6.
Changes From Protocol-Specified Efficacy Analyses............................................................................30
7.
SAFETY ANALYSES........................................................................................................................................31
7.1.
Adverse Events and Deaths....................................................................................................................31
7.1.1.
Adverse Event Dictionary ....................................................................................................31
7.1.2.
Adverse Event Severity........................................................................................................31
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................31
7.1.4.
Serious Adverse Events........................................................................................................31
7.1.5.
Treatment-Emergent Adverse Events...................................................................................32
7.1.6.
Summaries of Adverse Events and Deaths...........................................................................32
7.1.7.
Adverse Events of Special Interest.......................................................................................34
7.2.
Laboratory Evaluations ..........................................................................................................................35
7.2.1.
Summaries of Numeric Laboratory Results .........................................................................35
7.2.2.
Graded Laboratory Values ...................................................................................................37
7.2.3.
Liver-related Laboratory Evaluations...................................................................................38
7.3.
Body Weight and Vital Signs.................................................................................................................39
7.4.
Prior and Concomitant Medications.......................................................................................................39
7.4.1.
Prior Medications .................................................................................................................39
7.4.2.
Concomitant Medications.....................................................................................................40
7.5.
Electrocardiogram Results .....................................................................................................................40
7.6.
Other Safety Measures ...........................................................................................................................41
7.7.
Changes From Protocol-Specified Safety Analyses...............................................................................41
8.
PHARMACOKINETIC (PK) ANALYSES........................................................................................................42
8.1.
PK Analysis Methods.............................................................................................................................42
9.
REFERENCES ...................................................................................................................................................43
10.
SOFTWARE.......................................................................................................................................................44
11.
SAP REVISION..................................................................................................................................................45
Appendix 1.
Schedule of Assessments........................................................................................................46
Appendix 2.
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) .......................51


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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
ANCOVA
Analysis of covariance
AST
aspartate aminotransferase
BLQ
below the limit of quantitation
BMI
body mass index
CFR
Code of Federal Regulations
CI
confidence interval
CK
creatine kinase
CCLE
chronic cutaneous lupus erythematosus
CLASI
Cutaneous Lupus erythematosus disease Area and Severity Index
CLE
cutaneous lupus erythematosus
CMH
Cochran-Mantel-Haenszel
CRF
case report form
CSR
clinical study report
CTCAE
Common Toxicity Criteria for Adverse Events
DILI
drug-induced liver injury
DLQI
Dermatology Quality of Life Index
DMARD
Disease-modifying antirheumatic drug
DMC
data monitoring committee
ECG
electrocardiogram
EDC
electronic data capture
ET
early termination
FAS
Full Analysis Set
Hb
hemoglobin
HLT
high-level term
ICH
International Conference on Harmonization (of Technical Requirements for Registration of 
Pharmaceuticals for Human Use)
IXRS
interactive voice or web response system
LLT
lower-level term
LOQ
limit of quantitation
MACE
major adverse cardiovascular event
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed-effects model for repeated measures
MST
MedDRA search term
PK
pharmacokinetic
PT
preferred term
PTM
placebo to match
Q1, Q3
first quartile, third quartile


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QRS
electrocardiographic deflection between the beginning of the Q wave and termination of the 
S wave representing time for ventricular depolarization
QT
electrocardiographic interval between the beginning of the Q wave and termination of the T wave 
representing the time for both ventricular depolarization and repolarization to occur
QTc
QT interval corrected for heart rate
QTcF
QT interval corrected for heart rate using Fridericia’s formula
RA
rheumatoid arthritis
RR
electrocardiographic interval representing the time measurement between the R wave of one 
heartbeat and the R wave of the preceding heartbeat
SAE
serious adverse event
SCLE
subacute cutaneous lupus erythematosus
SAP
statistical analysis plan
SD
standard deviation
SI (units)
international system of units
SLE
systemic lupus erythematosus
SMQ
Standardized Medical Queries
SOC
system organ class
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
TSQM
Treatment Satisfaction Questionnaire for Medication
ULN
upper limit of normal
VAS
visual analog scale
VR
ventricular rate
WHO
World Health Organization


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PHARMACOKINETIC ABBREVIATIONS
AUClast
area under the concentration versus time curve from time zero to the last quantifiable concentration
AUCtau
area under the concentration versus time curve over the dosing interval
Clast
last observed quantifiable concentration of the drug 
Cmax
maximum observed concentration of drug 
Ctau
observed drug concentration at the end of the dosing interval
CLss/F
apparent oral clearance after administration of the drug:
at steady state: CLss/F = Dose/AUCtau , where “Dose” is the dose of the drug
t1/2
estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 2 
by the terminal elimination rate constant (z)
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
z
terminal elimination rate constant, estimated by linear regression of the terminal elimination phase 
of the concentration of drug versus time curve


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study report (CSR) 
for Study GS-US-436-4092. This SAP is based on the study protocol amendment 4 dated 
15 October 2018 and the electronic case report form (eCRF). The SAP will be finalized before 
the database freeze for the primary analysis. Any changes made after the finalization of the SAP 
will be documented in the CSR.
1.1.
Study Objectives
The primary objective of this study is as follows:

To evaluate the efficacy of filgotinib and lanraplenib in female subjects with moderately-to-
severely active CLE
The secondary objectives of this study are as follows:

To evaluate the safety and tolerability of filgotinib and lanraplenib in moderately-to-severely
active CLE
The exploratory objectives of this study are as follows:
 
 
 
1.2.
Study Design
This is a Phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety and 
efficacy of filgotinib and lanraplenib in female subjects with moderately-to-severely active CLE.
CCII 
I 
I 
I 
I 


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A schematic of this study is as below:
Eligible subjects will be randomized 2:2:1 in a blinded fashion to 1 of 3 arms and receive daily 
oral doses of the following study drugs starting on Day 1 for 12 weeks: 
Table 1.
Study Treatments
Arm
Study Drugs
Filgotinib 200 mg (n=20)
filgotinib 200 mg + PTM lanraplenib 30 mg
Lanraplenib 30 mg (n=20)
lanraplenib 30 mg + PTM filgotinib 200 mg
Placebo (n=10)
PTM filgotinib 200 mg + PTM lanraplenib 30 mg
PTM = placebo to match
On Day 1, randomization will be stratified by two factors: (i) disease subtype (chronic cutaneous 
lupus erythematosus [CCLE] (eg, discoid lupus erythematosus [DLE]) vs. subacute cutaneous 
lupus erythematosus [SCLE]) and (ii) concurrent background disease-modifying antirheumatic 
drug [DMARD] use vs. no use. 
At Week 12, upon completion of all scheduled assessments, subjects in placebo group will be 
re-randomized to receive filgotinib 200 mg + PTM lanraplenib 30 mg once daily or lanraplenib 
30 mg + PTM filgotinib 200 mg once daily for the remainder of the study in a blinded fashion. 
Dosing and assessments for all subjects will continue through Week 24.
Subjects who have not permanently discontinued study drug dosing during the first 24-week 
period may enter the subsequent 24-week extension period where they will continue to receive 
their assigned dose of study drug, in a blinded fashion.
Ser 
Randomiz~tion 
2:2:1 
17 
1° Endl)Oin 
PT 
group 
~• ndomrUbOO 
1:1 
V 
24 
ee 48 
FolowUp 


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1.3.
Sample Size and Power
With a sample size of 50 subjects (20 in each active treatment arm and 10 in the placebo arm), 
there is a 79% power to detect a 2 point difference between each active arm and the placebo arm 
in the primary endpoint,  change from baseline in CLASI activity score at week 12, using a 
2-sided 0.1 level test. This power calculation assumes a common standard deviation of 2 and a 
10% drop-out rate per arm. 


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2.
TYPE OF PLANNED ANALYSES
2.1.
Interim Analyses
2.1.1.
External Safety DMC
An external multidisciplinary Data Monitoring Committee (DMC) will review the progress of 
the study and perform interim reviews of the safety data in order to protect subject welfare and 
preserve study integrity. To ensure the best interests of the participants, the DMC will
recommend to the sponsor if the nature, frequency, and severity of adverse effects associated 
with the study treatment warrant the early termination of the study, the continuation of the study, 
or the continuation of the study with modifications.
The initial review will be conducted after 50% of subjects have completed 12 week of treatment
or have discontinued study early. Additional meetings may be scheduled as necessary.
The DMC’s role and responsibilities and the scope of analysis to be provided to the DMC are 
stated in a mutually agreed upon charter, which defines the DMC membership, meeting logistics, 
and meeting frequency.
2.1.2.
Internal Data Monitoring
To assess the safety and efficacy of lanraplenib and filgotinib for further planning and 
development of these products, a Gilead internal unblinded team independent of the blinded 
study team will be assembled. This group will consist of at least one representative from Clinical 
Research, Biostatistics, and Pharmacovigilance/Epidemiology, and may include other personnel 
as necessary. The Gilead internal unblinded team will be granted access to unblinded clinical 
data including treatment assignments to closely monitor study progress and drug safety. The 
membership, responsibilities, conduct, specific activities and meeting schedule of the unblinded 
internal team will be documented in a Gilead Internal Unblinded Team Charter. 
To mitigate the risks of inadvertently releasing the treatment information to the sites and 
subjects, the internal team will keep the unblinded information confidential and will not 
communicate the information to the blinded study team, site staff or subjects. Data unblinding 
due to medical emergency will follow standard Gilead procedures.
2.2.
Primary (Week 12) Analysis
A planned Week 12 analysis will be conducted after all subjects have either completed the
Week 12 visit or have prematurely discontinued from the study. 
A pre-specified sponsor team (members are not actively involved in the conduct of the study) 
will review the Week 12 unblinded safety and efficacy analysis results. A memo and a list will 
be maintained which documents the individuals granted access to the Week 12 unblinded results 
along with the justification for unblinding in accordance with Gilead SOPs. The Interim Analysis 
Data Integrity and Communication Plan will be developed prior to unblinding. The Study 
Management Team members with direct involvement in the conduct of the study will remain 


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blinded to treatment assignments throughout the trial, until all subjects have completed all 
planned study visits and the database has been locked.  
All planned analyses of the placebo-controlled period described in this SAP will be provided to 
the Designated Unblinded Study team (see the Data Integrity and Communication Plan) and will 
contain individual subject treatment assignments.
The following primary and secondary analysis reports and summaries may be provided to the 
project planning team (specified Gilead executives and the designated study team members): 

Demographics (Total column only)

Baseline characteristics (Total column only)

Disposition (Total column only)

Primary Analysis – Change from Baseline in CLASI-A at Week 12

Secondary Endpoints Analysis - Categorical changes in CLASI-A at Week 12

Other analysis as deemed necessary for program planning purposes
These reports will contain unblinded treatment group level information (not the individual 
subject treatment assignments). 
2.3.
Final Analysis
After all subjects have completed the study or discontinue early, outstanding data queries have 
been resolved or adjudicated as unresolvable, and the data have been cleaned and finalized, the 
study blind will be broken and the final analysis of the data will be performed.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard error (SE), median, first 
quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
All statistical tests will be 2-sided and performed at the 0.1 significance level unless otherwise 
specified.
By-subject listings will be presented for all subjects in the All Randomized Analysis Set and 
sorted by subject ID number, visit date, and time (if applicable). Data collected on log forms, 
such as adverse events, will be presented in chronological order within the subject. The treatment 
group to which subjects were randomized will be used in the listings. Age, sex at birth, race, and 
ethnicity will be included in the listings, as space permits.
3.1.
Analysis Sets
Analysis sets define the subjects to be included in an analysis. Analysis sets and their definitions 
are provided in this section. Subjects included in each analysis set will be determined before the 
study blind is broken for analysis. The analysis set will be identified and included as a subtitle of 
each table, figure, and listing.
For each analysis set, the number and percentage of subjects eligible for inclusion, as well as the 
number and percentage of subjects who were excluded with the reasons for their exclusion, will 
be summarized by treatment group.
A listing of reasons for exclusion from analysis sets will be provided by subject.
3.1.1.
All Randomized Analysis Set
All Randomized Analysis Set includes all subjects who were randomized in the study. This is the 
primary analysis set for by-subject listings.
3.1.2.
Full Analysis Set
The Full Analysis Set (FAS) includes all subjects who were randomized and received at least one 
dose of study drug (filgotinib, lanraplenib or placebo). This is the primary analysis set for 
efficacy analyses.  
3.1.3.
Safety Analysis Set
The Safety Analysis Set includes all subjects who received at least 1 dose of study drug. This is 
the primary analysis set for safety analyses.
3.1.4.
Per-Protocol Analysis Set
The per-protocol analysis will not be performed due to a limited number of subjects in the study.


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3.1.5.
Pharmacokinetic Analysis Set
The Pharmacokinetic (PK) Analysis Set will include all randomized subjects who took at least 
1 dose of study drug and have at least 1 non-missing post-dose concentration value reported by 
the PK laboratory. This is the primary analysis set for all PK analyses. Within the PK Analysis 
Set, those subjects with PK exposure data successfully derived from the population PK modeling 
(if applicable) will be included in the analyses related to PK exposure.
3.1.6.
Biomarker Analysis Set
The primary analysis set for biomarker analyses will be the Biomarker Analysis Set, which 
includes all randomized subjects who received at least one dose of study drug and have at least 
one baseline measurement available for the specific parameter of interest.
3.2.
Subject Grouping
In the FAS and PP Analysis Set, subjects will be grouped according to the treatment to which 
they were initially randomized at Study Day 1. For the analyses based on the Safety Analysis 
Set, subjects will be grouped according to the actual treatment that they received. The actual 
treatment received will be considered to differ from the randomized treatment only when 
subject’s actual treatment differs from randomized treatment for the entire treatment period.
For the analysis of the placebo-controlled period (up to week 12), subjects will be presented by 
three treatment groups: 

Filgotinib 200 mg

Lanraplenib 30 mg

Placebo
For the analyses for the entire study duration, subjects will be grouped into five treatment groups 
as specified in Table 2.
Table 2.
Treatment Groups for the Entire Study Duration
Lanraplenib 30 mg
Lanraplenib 30 mg from Study Day 1   
Filgotinib 200 mg
Filgotinib 200 mg from Study Day 1   
Placebo/Lanraplenib 30 mg
Placebo up to Week 12 and lanraplenib 30 mg after Week 12
Placebo/Filgotinib 200 mg
Placebo up to Week 12 and filgotinib 200 mg after Week 12
Placebo
Placebo group with study drug withdrawn prior to or at Week 12 (did not receive 
drug assigned at Week 12)
For the PK analyses, subjects will be grouped according to the actual treatment they received.


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3.3.
Strata and Covariates
Subjects will be randomly assigned to treatment groups via the interactive voice or web response 
system (IXRS) in a 2:2:1 ratio to lanraplenib 30 mg, filgotinib 200 mg and placebo using a 
stratified randomization schedule. Stratification will be based on the following variables:

Disease subtype (chronic cutaneous lupus erythematosus [CCLE] vs subacute cutaneous 
lupus erythematosus [SCLE]) 

Concurrent background systemic disease-modifying antirheumatic drug [DMARD] use 
For the stratification, systemic DMARDs administration will be considered. If there are 
discrepancies in stratification factor values between the IXRS and the clinical database, the 
values recorded in the clinical database will be used in the analyses. If it is impossible to derive 
the stratification factor from the clinical database due to missing values then the data from IXRS 
will be used. 
Efficacy endpoints will be evaluated using stratification factors as covariates or stratification 
variables for analyses, as specified in Section 6. 
For efficacy endpoints, the baseline value of the efficacy variable(s) will be included as a 
covariate in the efficacy analysis model.
3.4.
Examination of Subject Subgroups
The primary and secondary efficacy endpoints will be examined using the following subgroups:

Age (< 50 years and 50 years)

Disease subtype (CCLE, SCLE) 

Concurrent background disease-modifying antirheumatic drug [DMARD] use at baseline 
(Yes, No)

Concurrent use of systemic (oral) corticosteroids at baseline (Yes, No)

Diagnosis of SLE (Yes, No)

Duration of the disease (<10 years, >= 10 years)

Baseline CLASI-A (<15, >=15)
The descriptive statistics for each treatment group within the corresponding subgroup will be 
provided. 
3.5.
Multiple Comparisons
All significance testing will be done at the significance level of 0.1 with no multiplicity 
adjustment in this proof-of-concept study, unless otherwise specified.


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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document.
For missing last dosing date of study drug, imputation rules are described in Section 4.2.1. The 
handling of missing or incomplete dates for AE onset is described in Section 7.1.5.2, and for
prior and concomitant medications in Section 7.4. Imputation rules adopted in the efficacy 
analyses are specified in Section 6.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data will be included in the data analysis.
3.7.
Data Handling Conventions and Transformations
In general, age (in years) on the date of the first dose of study drug will be used for analyses and 
presentation in listings. If an enrolled subject was not dosed with any study drug, the 
randomization date will be used instead of the first dosing date of study drug. For screen failures, 
the date the informed consent was signed will be used for age calculation. If only the birth year is 
collected on the CRF, “01 July” will be used for the unknown birth day and month for the 
purpose of age calculation. If only birth year and month are collected, “01” will be used for the 
unknown birth day.
Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ)
or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summary statistics. An exception to this rule is any value reported as < 1 or < 0.1, 
etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).
Natural logarithm transformation will be used for plasma/blood concentrations and analysis of 
PK parameters. Plasma concentration values that are below the limit of quantitation (BLQ) will 
be presented as “BLQ” in the concentration data listing. Values that are BLQ will be treated as 0 
at predose time points, and one-half the value of the LOQ at postbaseline time points.


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The following conventions will be used for the presentation of summary and order statistics:

If at least 1 subject has a concentration value of BLQ for the time point, the minimum value 
will be displayed as “BLQ.”

If more than 25% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.”

If more than 50% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.”

If more than 75% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.”

If all subjects have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) will be displayed as “BLQ.”
PK parameters that are BLQ will be imputed as one-half LOQ before log transformation or 
statistical model fitting.
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the first dosing date of study drug and derived as follows:

For post dose study days: Assessment Date – First Dosing Date + 1

For days prior to the first dose: Assessment Date – First Dosing Date
Therefore, Study Day 1 is the day of the first dose of any study drug.
For placebo subjects who were re-randomized to active treatment at Week 12, the 
On-Active-Treatment study day will be calculated as: Assessment Date – Date of the first dose 
of active treatment + 1. The date of the first dose of the study drug dispensed at Week 12 is 
recorded on CRF.  
3.8.2.
Analysis Visit Windows
The target study days for analysis visits are provided in the Table 3 below: 


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Table 3.
Target Days for Analysis Visits
Nominal Visit
Nominal Study Day/
Study Day on Active Treatment
Screening
< 1
Baseline
<=1
Week 2
15
Week 4
29
Week 8
57
Week 12
85/1
Week 14
99/15
Week 16
113/29
Week 20
141/57
Week 24
169/85
Week 30
211/127
Week 36
253/169
Week 42
295/211
Week 48
337/253
Follow-up Visit
NA
The nominal visit as recorded on the CRF will be used when data are summarized by visit. 
Any data recorded under unscheduled visits will not be assigned to a particular visit or time 
point. However, the following exceptions will be made:

An unscheduled visit prior to the first dosing of study drug may be included in the calculation 
of the baseline value, if applicable

Unscheduled visits after the first dose of study drug will be included in determining the 
maximum postbaseline toxicity grade in safety analyses.
For subjects who prematurely discontinue from the study, early termination (ET) data will be 
assigned to what would have been the next scheduled visit where the respective data were 
scheduled to be collected.
Data collected at a follow-up visit will be summarized as a separate visit, and labeled “Follow-up 
Visit.”
Data obtained after the follow-up visit or last dose date plus 30 days (whichever is later) will be 
excluded from the summaries, but will be included in the listings.


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3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value.
If multiple valid, nonmissing, continuous measurements are recorded for the same visit, records 
will be chosen based on the following rules if a single value is needed:

In general, the baseline value will be the last nonmissing value on or prior to the first dosing 
date of study drug (Study Day 1), except for the analyses of active treatment period where 
the first dosing date of the active drug will be used. If multiple measurements occur on the 
same day, the last nonmissing value on or prior to the date of first dosing of study drug will 
be considered as the baseline value. If time is available, then use date and time to select the 
records with the latest time for the date. When times of these multiple measurements are not 
available, the average of these measurements (for continuous data) will be considered as the 
baseline value.  

For postbaseline values:
The record closest to the target day for that visit will be selected.
If there are 2 records that are equidistant from the target day, the later record will be 
selected.
If there is more than 1 record on the selected day and time is not collected then the 
average will be taken, unless otherwise specified.
If multiple valid, nonmissing, categorical measurements exist for the same visit, records will be 
chosen based on the following rules if a single value is needed:

For baseline, the last available record on or prior to the date of the first dose of study drug 
will be selected. If there are multiple records with the same time or no time recorded on the 
same day, the value with the lowest severity will be selected (eg, normal will be selected over 
abnormal for safety electrocardiogram [ECG] findings).

For postbaseline visits
The record closest to the target day for that visit will be selected
If there are 2 records that are equidistant from the target day, the later record will be 
selected.
If there are multiple records with the same time or no time recorded on the same day, the 
value with the worst severity within the window will be selected (eg, abnormal will be 
selected over normal for safety ECG findings).
All records will be listed by collection date.


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3.9.
Efficacy Estimands
Three efficacy estimands, a treatment-policy estimand and a hypothetical estimand are defined 
for the primary efficacy endpoint.
The treatment-policy estimand is the primary estimand for the primary endpoint.
1) Population: Subjects in the FAS
2) Variable: Primary and secondary endpoints 
3) Intercurrent events: The occurrence of an intercurrent event is irrelevant. All observed values 
will be used regardless of occurrence of an intercurrent event
4) Population-level summary: The difference in adjusted means of change from baseline for the 
continuous primary endpoint, difference in proportions between each active treatment group 
and placebo group for the binary efficacy endpoints
The hypothetical estimand is defined as following. This is the supportive estimand for the 
primary efficacy endpoint.
1) Population: Subjects in FAS
2) Variable: Primary endpoint 
3) Intercurrent events: The following intercurrent events are taken into account:
Subject takes prohibited medication
The dose of the medication required to be stable through Week 12 is changed at any time 
during the study
Subject discontinues from study treatment
4) Population-level summary: The difference in adjusted mean change from baseline.
The estimators associated with each of these estimands are described in Section 6.


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by initially randomized treatment group for 
each country, investigator within a country, and overall. The summary will present the number 
and percentage of subjects enrolled. For each column, the denominator for the percentage 
calculation will be the total number of subjects analyzed for that column.
A similar enrollment table will be provided by randomization stratum. The denominator for the 
percentage of subjects in the stratum will be the total number of enrolled subjects. If there are 
discrepancies in the value used for stratification assignment between the IXRS and the clinical 
database, the value collected in the clinical database or other source document will be used for 
the summary. A listing of subjects with discrepancies in the value used for stratification 
assignment between the IXRS and the clinical database or other source document at the time of 
data finalization will be provided.
The randomization schedule used for the study will be provided as an appendix to the CSR.
A summary of subject disposition will be provided by treatment group for both the entire study 
duration and by treatment phase. This summary will present the number of subjects in each of 
the categories listed below:

Subjects screened

Subjects randomized

Safety Analysis Set 

Completed Study

Prematurely discontinued study with reasons for discontinuation 

Completed study drug

Prematurely discontinued study drug with reasons for discontinuation 
The study and drug disposition will also be presented by study period with the following 
categories:

Completed study up to Week 12, Week 24, and through the end of the study

Completed study drug up to Week 12, Week 24, and through the end of study

Did not complete the study/study drug up to Week 12, Week 24, and through the end of 
study with reasons for premature discontinuation of the study/study drug

Re-randomized

Continuing study drug (Week 12 analysis only)

Continuing study (Week 12 analysis only)


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For the status of study drug and study completion and reasons for premature discontinuation with 
the number and percentage of subjects in each category will be provided. The denominator for 
the percentage calculation will be the total number of subjects in the Safety Analysis Set 
corresponding to that column. In addition, a flowchart will be provided to depict the disposition.
For placebo subjects, completion of the study up to Week 12 will be based on the presence of the 
corresponding visit in EDC or presence of Early termination visit which is after Week 8 visit and 
the [date of ET visit – date of first dose + 1] >= 82 days (target date for Week 12 visit – protocol 
allowed visit window). Subjects are considered to complete 12 weeks of treatment if the start 
date of Week 12 treatment is provided or the [last dose date – first dose date +1] >= 82.
The by-subject listing of disposition will be provided by subject identification (ID) number in 
ascending order to support the above summary tables.
4.2.
Extent of Study Drug Exposure and Adherence
Extent of exposure to study drug will be examined by assessing the total duration of exposure to 
study drug and the level of adherence to the study drug specified in the protocol.
4.2.1.
Duration of Exposure to Study Drug
Total duration of exposure to study drug will be defined as last dosing date of any study drug
minus first dosing date of any study drug plus 1, regardless of any temporary interruptions in 
study drug administration, and will be expressed in weeks using up to 1 decimal place 
(eg, 4.5 weeks). For Week 12 primary analysis, the data cut-off date can be used as the last 
dosing date for subjects continuing on study.  
For subjects with a partial last dosing date (ie, month and year of last dose are known), the latest 
of the dispensing dates of study drug bottles,  and the imputed last dose date [day imputed as last 
day of the month] will be used as the final imputed last dose date. 
If only year is recorded (ie, month and day of last dose are missing) or the entire date is missing 
then the latest of the dispensing month of study drug bottles, study drug start month, and study 
drug bottle return month will be used to impute the unknown last dose month (and a year if the 
entire date is missing). With the month imputed, the aforementioned method will be used to 
impute the last dose date. If the imputed date is after the date of death, choose the death date.
In addition, the duration of active treatment will be provided. The calculation for the subjects 
originally randomized to placebo will include the period starting from the first day of active 
study drug (Week 12 treatment start date is recorded on CRF).
The total duration of exposure to study drug will be summarized using descriptive statistics
(number of subjects [n], mean, SD, median, Q1, Q3, minimum, and maximum) and the 
percentage of subjects exposed through the following time periods: Day 1, Weeks 2, 4, 8, 12, 14, 
16, 20, 24, 30, 36, 42, and 48. The subject is considered to be exposed up to Week X if the last 
dose of any study drug is at least visit target day (per Table 3) minus protocol-allowed window 
(protocol Appendix 2).
Summaries will be provided by treatment group for the Safety Analysis Set. No formal statistical 
testing is planned.


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4.2.2.
Adherence to Study Drug
The total number of doses administered will be summarized using descriptive statistics for each 
study drug. 
The presumed total number of doses administered to a subject will be determined by the data 
collected on the drug accountability CRF using the following formula:
Total Number of Doses Administered =
No. of Doses Dispensed
No. of Doses Returned















If a bottle is dispensed and returned empty, then the number of tablets returned will be entered as 
zero. If a bottle is dispensed but not returned (missing) then the number of tablets from that 
bottle will be counted as zero.
If calculated adherence is greater than 100%, the result will be set to 100%.
The adherence will be calculated separately for each treatment administered: filgotinib 
200 mg/PTM or lanraplenib 30 mg/PTM. The overall adherence will be lowest of the two.  
4.2.2.1.
Prescribed Adherence
The level of prescribed adherence to the study drug regimen will be determined by the total 
amount of study drug administered relative to the total amount of study drug specified by the 
protocol for a subject who completes treatment in the study.
The level of prescribed adherence will be expressed as a percentage using the following formula:
Total Amount of Study Drug Administered
Prescribed Adherence (%) =
 x 100
Total Amount of Study Drug Specified by Protocol






Descriptive statistics for the level of prescribed adherence up to Week 12, up to Week 24 and the 
entire study duration with the number and percentage of subjects belonging to adherence 
categories: < 80, ≥ 80% will be provided by treatment group for the Safety Analysis Set. 
The expected amount of study drug to be administered is derived as:

up to Week 12 is 84 (7 * 12) doses

up to Week 24 is 168 (7 * 24) doses

Entire study  is 336 (7 * 48) doses 


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The total amount of study drug administered up to week 12/24 will be calculated based on the 
drug accountability reported on CRF: (total pills dispensed – total pills returned) up to 
Week 12/24 visit.
No formal statistical testing is planned.
By-subject listings of study drug administration and accountability will be provided separately
by subject ID number in ascending order and in chronological order for each treatment 
separately.
4.3.
Protocol Deviations 
Subjects who did not meet the eligibility criteria for study entry, but enrolled in the study, will be 
summarized. The summary will present the number and percentage of subjects who did not meet 
at least 1 eligibility criterion and the number of subjects who did not meet specific criteria by 
treatment group based on the All Randomized Analysis Set. A by-subject listing will be provided 
for those subjects who did not meet at least 1 eligibility (inclusion or exclusion) criterion. The 
listing will present the eligibility criterion (or criteria if more than 1 deviation) that subjects did 
not meet and the related comments, if collected.
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. The number and percentage of subjects with important protocol deviations by 
deviation reason (eg, violation of select inclusion/exclusion criteria) will be summarized by 
treatment group for the Safety Analysis Set. A by-subject listing will be provided for the subjects 
with important protocol deviations.


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5.
BASELINE CHARACTERISTICS  
5.1.
Demographics
Subject demographic variables will be summarized by treatment group and overall using 
descriptive statistics for continuous variables, and using number and percentage of subjects for 
categorical variables. The summary of demographic data will include the following:

age (on the first dose date of any study drug) as a continuous variable

age group (< 50, ≥ 50 years)

race 

ethnicity (Hispanic or Latino, not Hispanic or Latino)
Subject demographic variables (i.e., age, sex, race, and ethnicity) will be summarized by 
treatment group and overall using descriptive statistics for age, and using number and percentage 
of subjects for sex, race, and ethnicity. The summary of demographic data will be provided for 
the Safety Analysis Set.
A by-subject demographic listing, including the informed consent date, will be provided by 
subject ID number in ascending order.
5.2.
Baseline Characteristics
The baseline characteristics include:

weight (kg)

body mass index (BMI; in kg/m2) 

CLE disease subtype (CCLE, SCLE) 

time from CLE diagnosis to enrollment (as continuous in years, < 10 and >= 10 years)

diagnosis of SLE (Yes, No)

diagnosis of RA (Yes, No)

diagnosis of Sjogren’s Syndrome (Yes, No)

concurrent background systemic DMARD use at baseline (Yes, No) 

concurrent background use of systemic (oral) corticosteroids (Yes, No)

concurrent background use of anti-malarial DMARD drugs (Yes, No)


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
baseline CLASI Activity score (as continuous variable, categories <15 and >=15)

baseline CLASI Damage score (as continuous variable, categories < 10 and >=10)

baseline subject’s global assessment of CLE activity (mm)

baseline physician’s global assessment of CLE activity (mm)
The time from CLE diagnosis will be calculated in years between the date of enrollment and the 
date of diagnosis. The missing month will be imputed with January, the missing day will be 
imputed with 1st day of the month.
The baseline characteristics will be summarized by treatment group and overall using descriptive 
statistics (n, mean, SD, median, Q1, Q3, minimum, and maximum) for continuous variables and 
using number and percentage for categorical variables. 
The summary of baseline characteristics will be provided for the FAS. No formal statistical 
testing is planned.
A by-subject listing of other baseline characteristics will be provided by subject ID number in 
ascending order.
5.3.
Medical History
Medical history will be collected at screening for CLE and other conditions.  
The medical history data will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).
Medical history data will be summarized by system organ class (SOC), preferred term (PT), 
treatment group, and overall. Subjects who report 2 or more medical history items that are coded 
to the same SOC and/or PT will be counted only once by the unique coded term in the summary. 
The summary will be provided for the Safety Analysis Set. No formal statistical testing is 
planned. 
The CLE-related medical history will be summarized by treatment group and overall by the 
number and percentage of subjects with each CLE subtype. 


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6.
EFFICACY ANALYSES
Efficacy endpoints will be evaluated for the following treatment periods: Placebo controlled 
period up to Week 12 and the entire study up to Week 48. 
For the binary variables, non-responder imputation will be used. For continuous variables,  
imputation will not be performed prior to MMRM analysis.
The primary endpoint will be analyzed based on the estimands presented in Table 4. 
Table 4.
Continuous 
Endpoint
Treatment Policy 
Hypothetical 
Population
FAS
FAS
Endpoint
Change from Baseline
Change from Baseline
Intercurrent Event
Ignore all intercurrent events
Treatment discontinuation
Start of prohibited medication
The dose change of medication that required 
to be stable 
Treat data as missing after the event.
Estimator
MMRM with no imputation of missing data 
MMRM with no imputation of missing data 
6.1.
Definition of the Primary Efficacy Endpoints
The primary efficacy endpoint for this study is the change in CLASI activity score from baseline 
to Week 12.
Activity score is the sum of the scores of the left side of the CLASI worksheet (i.e. for erythema, 
scale/hypertrophy, mucous membrane involvement and alopecia. See Appendix 2). The activity 
score ranges from 0 to 70 with higher score indicating more severe skin disease.
6.2.
Analysis of the Primary Efficacy Endpoint
The primary analyses will be a test of superiority with the null hypotheses below:

H01:  There is no difference between filgotinib 200 mg and placebo in the change in CLASI 
activity score from baseline to Week 12

H02:  There is no difference between lanraplenib 30 mg and placebo in the change in CLASI 
activity score from baseline to Week 12
The primary endpoint will be analyzed using a mixed-effects repeated measures (MMRM) 
model. The model may include terms for baseline CLASI-A value, treatment, stratification 
factors (disease subtype, and concurrent background DMARD use), visit, and treatment-by-visit 


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interaction. Subject will be included as a random effect. The Kenward-Roger method will be 
used to estimate the degrees of freedom. The two treatment comparisons versus placebo will be 
done separately at the 2-sided 0.1 level. The unstructured (UN) variance-covariance matrix of 
repeated measures will be considered first. If model does not converge then ARH(1) structure 
will be applied.
The primary analysis will be based on the treatment policy estimand. The described analysis is 
the main estimator for the primary endpoint.
Descriptive statistics (n, mean, SD, median, Q1, Q3, minimum, and maximum) will be presented 
in the descriptive summaries. Adjusted means and 95% confidence intervals (CIs) will also be 
provided for each visit and treatment group.
Descriptive statistics of change from baseline in CLASI-A at Week 12 will be presented for the 
subgroups specified in Section 3.4. 
The line plots for median (Q1, Q3) change (absolute and percent) in CLASI-A from baseline, 
mean (+/- 95% CI) change from baseline, and the adjusted estimates of mean change from 
baseline (+/- 95% CI) will be provided.
A plot of cumulative distribution of change from baseline in CLASI-A at Week 12 will be 
presented by treatment group on the observed data. 
6.3.
Sensitivity Analysis of Primary Endpoint
The following sensitivity analyses of the primary endpoint (Change in CLASI-A total score at 
Week 12) will be performed:

primary analysis repeated on hypothetical estimand 

non-parametric ANCOVA analysis using rank transformed data
6.4.
Secondary Efficacy Endpoints
6.4.1.
Definition of Secondary Efficacy Endpoints
Secondary efficacy endpoints include:

Proportion of subjects at Week 12 with a decrease of ≥ 5 points in CLASI activity score from 
baseline 

Proportion of subjects at Week 12 with no worsening in CLASI activity score from baseline 
(worsening defined as ≥ 3 point increase)

Proportion of subjects at Week 24 with a decrease of ≥ 5 points in CLASI activity score from 
baseline 

Proportion of subjects at Week 24 with no worsening in CLASI activity score from baseline 
(worsening defined as ≥ 3 point increase)


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6.4.2.
Analysis Methods for Secondary Efficacy Endpoint
The proportion of subjects with a decrease of ≥ 5 points in CLASI activity score and the 
proportion of subjects with no worsening from baseline to Week 12 will be analyzed separately 
using Cochran-Mantel-Haenszel (CMH) test stratified by the randomization stratification factors. 
If stratification leads to small cell sizes, the strata will be pooled and the Fisher’s Exact test will 
be used.
The proportion of subjects with a decrease of ≥ 5 points in CLASI activity score from baseline to 
Week 24 and no worsening in CLASI-A from baseline to Week 24 will be analyzed by one-
sample exact binomial test for each active treatment group.
The number and percentage of subjects with a decrease of ≥ 5 points in CLASI activity score 
from baseline and no worsening at Week 12 and at Week 24 will be provided.  95% CIs for the 
percentage will be calculated using the Clopper-Pearson exact method.
The secondary endpoints analysis will be based on the FAS. The missing response data will be 
imputed as No Response. The sensitivity analysis without imputation of the missing values 
(observed cases) will also be performed.
6.5.
Exploratory Efficacy Endpoints
6.5.1.
Definition of Exploratory Efficacy Endpoints
Exploratory efficacy endpoints include:  
 
 
 
 
 
 
 
 
 
 
 
CCII 
I 
I 
I 
I 
I 


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6.5.2.
Analysis Methods for Exploratory Efficacy Endpoints
 
 
 
 
  
CCI
CCI
CCI
I 
I 


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6.6.
Changes From Protocol-Specified Efficacy Analyses
The treatment policy and hypothetical estimands have been added to the analyses of the primary 
endpoint.
CCI


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7.
SAFETY ANALYSES
The safety analyses will be performed for the placebo-controlled treatment period up to 
Week 12, up to Week 24, and for the entire study duration. Analyses for these treatment periods
will be presented by the treatment groups specified in Section 3. 
For the analyses of adverse events that include data after Week 12 the exposure-adjusted 
analyses will be presented.
For the AEs, laboratory abnormalities and concomitant medication data, the collection/start date 
will be used to determine which reporting period the record belongs to. For other parameters, the 
nominal visits will be used.
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of 
MedDRA. System organ class (SOC), high-level group term (HLGT), high-level term (HLT), 
preferred term (PT), and lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to toxicity 
criteria specified in the protocol (CTCAE 4.03). The severity grade of events for which the 
investigator did not record severity will be categorized as “missing” for tabular summaries and 
data listings. The missing category will be listed last in summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE CRF to the 
question of “Related to filgotinib/placebo” or “Related to lanraplenib/placebo”. If AE is reported 
as “Related” to any of 2 study drugs then the AE is considered “Related to study treatment”. 
Relatedness will always default to the investigator’s choice, not that of the medical monitor. 
Events for which the investigator did not record relationship to study drug will be considered 
related to study drug for summary purposes. However, by-subject data listings will show the 
relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs captured and stored in the 
clinical database will be reconciled with the SAE database from the 
Pharmacovigilance & Epidemiology Department before data finalization.


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7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) of the entire study duration are defined as 1 or both 
of the following:

Any AEs with an onset date on or after any study drug start date and no later than 30 days 
after permanent discontinuation of any study drug

Any AEs leading to premature discontinuation of study drug.
TEAEs up to Week12/24 are defined as 1 or both of the following:

Any AEs with an onset date on or after Day 1, prior to start of Week 12/24 treatment and no 
later than the day before the Week 12/24 treatment start date. For subjects who discontinued 
treatment prior to Week 12/24 visit, any AEs with an onset date on or after the study drug 
start date and no later than 30 days after permanent discontinuation of study drug 

Any AEs leading to premature discontinuation of study drug prior to first Week 12/24 dosing
7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The AE onset is the same as or after the month and year (or year) of the first dosing date of 
study drug, and

The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to 30 days after the date of the last dose of study drug
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, will be considered to be treatment emergent. In 
addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dosing date of study drug will 
be considered treatment emergent.
7.1.6.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set. The tables will 
be presented by treatment period: placebo-controlled period (up to Week 12) and for weeks 
12-48. The overall summary of TEAEs may also be provided for the entire study duration.


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The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, HLT, PT, and treatment group. For other AEs described below, summaries 
will be provided by SOC, PT, and treatment group:

All TEAEs

TEAEs of Grade 3 or higher (by maximum severity)

All TE treatment-related AEs

TE treatment-related AEs of Grade 3 or higher (by maximum severity)

All TE SAEs

All TE treatment-related SAEs 

All TEAEs leading to premature discontinuation of study drug

All TEAEs leading to premature discontinuation of study

All TEAEs leading to death (i.e. outcome of death)
A brief, high-level summary of AEs described above will be provided by treatment group and by 
the number and percentage of subjects who experienced the above AEs. All deaths observed in 
the study will also be included in this summary.
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC and HLT within each SOC (if applicable), 
and then by PT in descending order of total frequency within each SOC. For summaries by 
severity grade, the most severe grade will be used for those AEs that occurred more than once in 
an individual subject during the study. 
In addition to the above summary tables, all TEAEs and TE treatment-related AEs will be 
summarized by PT only, in descending order of total frequency.
The data listings will be provided for the following:

All AEs, indicating whether the event is treatment emergent

All AEs of Grade 3 or higher

SAEs

Deaths

AEs leading to premature discontinuation of study drug

AEs leading to premature discontinuation of study


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7.1.7.
Adverse Events of Special Interest
Events of interest will be identified by the use of either SMQs or MSTs. However, should 
additional cases not detected by the predefined search term listings be identified during the 
clinical review process, these cases will also be reported by respective category. Serious major 
adverse cardiovascular events (MACE) will not be adjudicated.   
Adverse events of special interest include:

All infections (defined as all PTs within the Infections and Infestations SOC)

Serious infections (defined as all PTs within the Infections and Infestations SOC that are 
SAEs)

Infections of special interest as defined below 
A) Herpes zoster
B) Active tuberculosis 
C) Opportunistic infections 
D) Hepatitis B or C (HBV and HCV) infections 

Venous thrombotic events and pulmonary embolism

Malignancies 

Gastrointestinal (GI) perforations 

Liver transaminase elevation

Serious potential major adverse cardiovascular events (MACE) defined by the following 
terms:
A) Cardiovascular events
B) Myocardial infarction
C) Hospitalization for unstable angina
D) Transient ischemic attack
E) Stroke
F) Hospitalization for cardiac failure
G) Percutaneous coronary intervention


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The number and percentage of patients with aforementioned events of special interest will be 
provided by the PT term.
A by-subject listing for all patients having AE of special interests at any time will be provided.
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to the last dose of study drug plus 30 days
for subjects who have permanently discontinued study drug, or all available data at the time of 
the database snapshot for subjects who were ongoing at the time of an interim analysis. The 
analysis will be based on values reported in conventional units. When values are below the LOQ, 
they will be listed as such, and the closest imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.7. Hemolyzed test results will not be 
included in the analysis, but they will be listed in by-subject laboratory listings.
A baseline laboratory value for the placebo-controlled and entire study period will be defined as 
the last nonmissing measurement obtained on or prior to the date/time of first dose of any study 
drug. For the active treatment period, the baseline for the subjects originally randomized to 
placebo will be the measurement before or on the day when the first dose of active study 
treatment is administered. 
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and urinalysis separately. Values falling 
outside of the relevant reference range and/or having a severity grade of 1 or higher on the 
Common Terminology Criteria for Adverse Events (CTCAE severity grade) will be flagged in 
the data listings, as appropriate.
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for the following laboratory tests:

Hematology
Hematocrit
Hemoglobin
Platelet count
Red blood cell count
White blood cell (WBC) count
Mean corpuscular volume


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Lymphocytes
Monocytes
Neutrophils
Eosinophils
Basophils

Chemistry
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Alkaline phosphatase (ALP)
Total bilirubin
Serum creatinine
Creatinine clearance by Cockcroft-Gault formula
Creatine phosphokinase (CPK)
Glucose

Lipid Panel
Triglycerides
Total cholesterol
HDL
LDL
LDL/HDL ratio
Fasting results for lipid profile and serum glucose will be presented separately from overall 
results. 
Change from baseline to a postbaseline visit will be defined as the visit value minus the baseline 
value. The mean, median, Q1, Q3, minimum, and maximum values will be displayed to the 
reported number of digits; SD values will be displayed to the reported number of digits plus 1.


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Median (Q1, Q3) of the observed values for the laboratory tests specified above will be plotted 
using a line plot by treatment group and visit.
In the case of multiple values within the visit, data will be selected for analysis as described in 
Section 3.8.3.
7.2.2.
Graded Laboratory Values
The CTCAE will be used to assign toxicity grades (0 to 4) to laboratory results for analysis. 
Grade 0 includes all values that do not meet the criteria for an abnormality of at least Grade 1. 
For laboratory tests with criteria for both increased and decreased levels, analyses for each 
direction (ie, increased, decreased) will be presented separately. 
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities for the entire study period and in subjects 
discontinued treatment prematurely are defined as values that increase at least 1 toxicity grade 
from baseline at any postbaseline time point, up to and including the date of last dose of study 
drug plus 30 days for subjects who permanently discontinued study drug, or the last available 
date in the database snapshot for subjects who were still on treatment at the time of an interim 
analysis. If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 
observed within the time frame specified above will be considered treatment emergent.
For the analyses of active treatment period, the baseline is the day of the first dose of active 
study drug administration. 
For the analyses of placebo-controlled period, the lab abnormality occurring after 
(within 30 days) Week 12 visit is included only if subject did not continue treatment after 
Week 12.  
The listing of all laboratory abnormalities will be provided. 
7.2.2.2.
Treatment-Emergent Marked Laboratory Abnormalities
Treatment-emergent marked laboratory abnormalities are defined as values that increase from 
baseline by at least 3 toxicity grades at any postbaseline time point, up to and including the date 
of the last dose of study drug plus 30 days for subjects who permanently discontinued study drug 
or the last available date in the database snapshot for subjects who were still on treatment at the 
time of an primary Week 12 analysis. If the relevant baseline laboratory value is missing, any 
Grade 3 or 4 values observed within the timeframe specified above will be considered 
treatment-emergent marked abnormalities.
Same rules as in the Section 7.2.2.1 apply for determination of TE abnormality in the 
placebo-controlled and entire study duration. 


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7.2.2.3.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; subjects will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:

Treatment-emergent laboratory abnormalities

Treatment-emergent grade 3 or 4 laboratory abnormalities

Treatment-emergent marked laboratory abnormalities
The summaries of treatment-emergent laboratory abnormalities will be presented by treatment 
group and highest grade for the placebo-controlled and active treatment period. The listing of all 
laboratory abnormalities will be provided.
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
nonmissing postbaseline values, with the baseline determined per Section 7.2.
By-subject listings of treatment-emergent Grade 3 or 4 laboratory abnormalities and marked 
laboratory abnormalities will be provided by subject ID number and visit in chronological order. 
This listing will include all test results that were collected throughout the study for the lab test of 
interest, with all applicable severity grades displayed.
7.2.3.
Liver-related Laboratory Evaluations
Liver-related abnormalities after initial study drug dosing will be examined and summarized 
using the number and percentage of subjects who were reported to have the following laboratory 
test values for postbaseline measurements:

Aspartate aminotransferase (AST): (a) > 3 times of the upper limit of reference range
(ULN); (b) > 5 x ULN; (c) > 10 x ULN; (d) > 20 x ULN

Alanine aminotransferase (ALT): (a) > 3 x ULN; (b) > 5 x ULN; (c) > 10 x ULN; (d) > 20 x 
ULN

AST or ALT: (a) > 3 x ULN; (b) > 5 x ULN; (c) > 10 x ULN; (d) > 20 x ULN

Total bilirubin: > 2 x ULN

Alkaline phosphatase (ALP) > 1.5 x ULN

AST or ALT > 3 x ULN and total bilirubin: (a) > 1.5 x ULN; (b) > 2 x ULN
The summary will include data from all postbaseline visits on active treatment up to 30 days 
after the last dose of study drug. For individual laboratory tests, subjects will be counted once 
based on the most severe postbaseline values. For both the composite endpoint of AST or ALT 
and total bilirubin, subjects will be counted once when the criteria are met at the same 


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postbaseline visit date. The denominator is the number of subjects in the Safety Analysis Set who 
have nonmissing postbaseline values of all relevant tests at the same postbaseline visit date. 
The analyses will be presented for the placebo-controlled period and entire study period. 
A listing of subjects who met at least 1 of the above criteria will be provided.
7.3.
Body Weight and Vital Signs
Descriptive statistics will be provided by treatment group for body weight, BMI and vital signs
(pulse rate, systolic and diastolic blood pressure, body temperature, and respiratory rate) as 
follows:

Baseline value

Values at each postbaseline visit

Change from baseline at each postbaseline visit
A baseline value will be defined as the last available value collected on or prior to the date of 
first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value. Body weight and vital signs measured at 
unscheduled visits will be included for the baseline value selection.
In the case of multiple values at the visit, data will be selected for analysis as described in
Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of vital signs will be provided by subject ID number and visit in 
chronological order. Body weight and BMI will be included in the vital signs listing, if space 
permits. If not, they will be provided separately.
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the Gilead-modified World Health Organization (WHO) Drug dictionary.
7.4.1.
Prior Medications
Prior medications are defined as any medications taken and stopped prior to the day the subject
took the first dose of study drug.
Prior medications will be summarized by each Anatomical Therapeutic Chemical (ATC) drug 
class level 2 and preferred name using the number and percentage of subjects for each treatment 
group and overall. A subject reporting the same medication more than once will be counted only 
once when calculating the number and percentage of subjects who received that medication. The 
summary will be ordered alphabetically by preferred term in order of descending overall 
frequency. For drugs with the same frequency, sorting will be done alphabetically.


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For the purposes of analysis, any medication with a stop date prior to the first dosing date of 
study drug will be included in the prior medication. If a partial stop date is entered the 
medication will be considered prior unless the month and year (if day is missing) or year (if day 
and month are missing) of the stop date are after the first dosing date. The medications taken for 
CLE or SLE will be considered prior per designation on CRF.
Summaries will be based on the Safety Analysis Set. No formal statistical testing is planned.
7.4.2.
Concomitant Medications
Concomitant medications are defined as medications taken on the date the subject first started 
study drug, or started after the date the subject first took study drug. Use of general and disease-
specific (for CLE or SLE) concomitant medications will be summarized by preferred name using 
the number and percentage of subjects for each treatment group. A subject reporting the same 
medication more than once will be counted only once when calculating the number and 
percentage of subjects who received that medication. The summary will be ordered 
alphabetically by preferred term in descending overall frequency. For drugs with the same 
frequency, sorting will be done alphabetically.
For the purposes of analysis, any medication with a start date prior to or on the first dosing date 
of study drug and continued to be taken after the first dosing date, or started after the first dosing 
date but prior to or on the last dosing date of study drug will be considered concomitant 
medication. Medications started and stopped on the same day as the first dosing date or the last 
dosing date of study drug will also be considered concomitant. Medications with a stop date prior 
to the date of first dosing date of study drug or a start date after the last dosing date of study drug 
will be excluded from the concomitant medication summary. 
If a partial stop date is entered, any medication with the month and year (if day is missing) or 
year (if day and month are missing) prior to the date of first study drug administration will be 
excluded from the concomitant medication summary. If a partial start date is entered, any 
medication with the month and year (if day is missing) or year (if day and month are missing) 
after the study drug stop date will be excluded from the concomitant medication summary. 
Medications with completely missing start and stop dates will be listed but not included in the 
concomitant medication summary, unless the medication is reported as ongoing. Summaries will 
be based on the Safety Analysis Set. No formal statistical testing is planned.
In addition, prior and concomitant medications for SLE and CLE will be presented in a separate
summary table by medication category, and preferred term.  
All prior and concomitant medications (other than per-protocol study drugs) will be provided in a 
by-subject listing sorted by subject ID number and administration date in chronological order
based on Safety Analysis Set.
7.5.
Electrocardiogram Results
A shift table of the investigators’ assessment of ECG results at each visit compared with baseline 
values will be presented by treatment group using the following categories: normal; abnormal, 
not clinically significant; abnormal, clinically significant; or missing. The number and 


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percentage of subjects in each cross-classification group of the shift table will be presented. 
Subjects with a missing value at baseline or postbaseline will not be included in the denominator 
for percentage calculation. No formal statistical testing is planned.
A by-subject listing for ECG assessment results will be provided by subject ID number and visit 
in chronological order.
7.6.
Other Safety Measures
A data listing will be provided for subjects who become pregnant during the study.
7.7.
Changes From Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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8.
PHARMACOKINETIC (PK) ANALYSES
Blood samples for PK analysis will be collected at Week 2 (at least 30 minutes and up to 3 hours 
postdose), anytime at Week 4, and within 2 hours prior to study drug administration at Weeks 12 
and 24.
Plasma concentrations of filgotinib, the active metabolite of filgotinib (GS-829845), and 
lanraplenib will be listed and summarized using descriptive statistics (eg, sample size, arithmetic 
mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and 
maximum).
8.1.
PK Analysis Methods
Individual subject concentration data and individual subject PK parameters for filgotinib, 
GS-829845, and lanraplenib will be listed and summarized using descriptive statistics by 
treatment. Summary statistics (number [n], mean, SD, coefficient of variation [%CV], median, 
min, max, Q1, and Q3) will be presented for individual subject concentration data by time point 
(Week 2, Week 12 and Week 24) and by treatment. For Week 12 and 24 samples, only samples 
collected 20 to 28 hours after the prior dose will be included in the summary statistics.
Individual concentration data listings and summaries will include all subjects with concentration 
data. The sample size for each time point will be based on the number of subjects with 
nonmissing concentration data at that time point. The number of subjects with concentration 
BLQ will be presented for each time point. For summary statistics, BLQ values will be treated as 
0 at predose and one-half of the lower limits of quantitation (LLOQ) for postdose time points. 


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9.
REFERENCES
Albrecht J et. al (2005) The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity 
Index): An Outcome Instrument for Cutaneous Lupus Erythematosus. J Invest Dermatol 125:889 
–894  
Rachel S. et. al (2010) Cutaneous Lupus and the CLASI Instrument. Rheum Dis Clin North Am.
2010 Feb 1; 36(1): 33–51.
Finlay AY and Khan GK. Dermatology Life Quality Index (DLQI): a simple practical measure 
for routine clinical use. Clin Exp Dermatol 1994; 19:210-216.
DLQI instructions for use and scoring. http://sites.cardiff.ac.uk/dermatology/quality-of-
life/dermatology-quality-of-life-index-dlqi/dlqi-instructions-for-use-and-scoring/


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10.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.
nQuery Advisor(R) Version X.0. Statistical Solutions, Cork, Ireland.


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11.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


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Appendix 1.
Schedule of Assessments
Study Procedures
Screena
Study Dosing Period
24-week Extension Period
ETc
F/Ud
Day 
1b
Week 
2
Week 
4
Week 
8
Week 
12
Week 
14
Week 
16
Week 
20
Week 
24
Week 
30
Week 
36
Week 
42
Week 
48
± 2 
days
± 3 
days
± 3 
days
± 3 
days
± 5 
days
± 5 
days
± 5 
days
± 5 
days
± 7 
days
± 7 
days
± 7 
days
± 7 
days
± 5 
days
± 5 
days
Written Informed 
Consent
X
Review of 
Inclusion/ 
Exclusion Criteria
X
Medical Historye
X
X
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Complete Physical 
Examination
X
Symptom-driven 
Physical 
Examinationf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signsg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physician’s Global 
Assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CLASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Detailed Target 
Lesion Assessmentv
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


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Photography of 
Areas with Skin 
Involvementw
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Detailed Mucous 
Membrane 
Assessmentx
X
X
X
X
X
X
X
Subject’s Global 
Assessment and 
other 
subject-reported 
measuresh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xi
12-lead ECG
X
X
X
X
Xy
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fasting Lipidsj
X
X
X
X
CRP and ESR
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HbA1c and TSH
X
Urinalysis and 
Urine protein to 
creatinine ratio
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Drug and 
Alcohol Screen
X
Serum Pregnancy 
Testk
X
Urine Pregnancy 
Testk, l
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
FSH Testm
X
HIV-1, HIV-2, 
HBV, HCV 
Serology
X


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HCV Monitoringn
X
X
X
X
Xy
Quantiferon Testo
X
Chest X-rayo
X
Quantitative Serum 
Immunoglobulin 
Test
X
X
X
X
Autoantibody Panel 
X
X
X
X
Complement Levels
X
X
X
X
X
X
Pharmacokineticsp
X
X
X
X
Whole Blood, 
Cytochex
X
Xs
X
X
X
X
X
Whole Blood, 
Heparin 
X
Xs
X
X
X
X
X
Serum biomarker 
sample
X
Xs
X
X
X
X
X
X
X
Plasma biomarker 
sample
X
Xs
X
X
X
X
X
X
X
vfPBMC
X
Xs
X
X
X
X
X
PAXgene RNA 
sample
X
Xs
X
X
X
X
X
X
X
Randomization
X
Xt
Study Drug 
Dispensing
X
X
X
X
X
X
Xu
X
X
X
Study Drug 
Accountability
X
X
X
X
X
X
X
X
X
X
X
X
X
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Filgotinib and Lanraplenib
Statistical Analysis Plan
GS-US-436-4092
Version 1.0
CONFIDENTIAL
Page 49
13 May 2019
Review AEs & 
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Prospective subjects should be screened no more than 28 days prior to randomization and administration of the first dose of study drugs.
b
Day 1 procedures, including study drug administration, will be performed at the study center. All assessments will be performed prior to dosing unless otherwise indicated.
c
Subjects who discontinue from the study prior to Week 24 (or prior to Week 48 for subjects entering the 24-week extension period), will return to the study center for ET 
assessments.
d
Subjects will return to the study center for a FU visit 4 weeks (± 5 days) after their last dose of study drug. Subjects who discontinue study drug ≥4 weeks prior to their 
last visit will not be asked to return for the FU visit.
e
At screening, medical history will include collection of demographics and a review of surgical history and CLE history (including documentation of prior skin biopsy results, 
if available). Medical history will be updated, as needed, on Day 1.
f
Symptom-driven physical examinations will be performed, as needed, based on signs and symptoms.
g
Vital signs include resting blood pressure, heart rate, respiratory rate, and temperature. 
h
Includes VAS (subject assessment of CLE on sexual activity; autoimmune disease-related dry eyes/mouth, body pain, joint pain/stiffness, and fatigue), SF-36, DLQI, and 
TSQM. Subject reported outcomes are recommended to be performed at the beginning of each visit prior to any other visit-related procedures (other than signing of informed 
consent). 
i
The TSQM will not be administered at the FU visit.
j
An overnight fast (no food or drinks, except water) of at least 8 hours is required prior to collection of blood samples for lipid testing.
k
Females of childbearing potential only (see Protocol Appendix 5). 
l
When visits are greater than 4 weeks apart, women should continue to have urine pregnancy tests every 4 weeks using at home pregnancy test kits that will be provided to 
them. The site will call the subject every 4 weeks to obtain results of these pregnancy tests and will record the information in the source documents and eCRF. If any urine 
pregnancy test is positive, study drug should be immediately interrupted and the subject should return to the study center for a serum pregnancy test.
m
Females of non-childbearing potential only (see protocol Appendix 5).
n
Viral monitoring for HCV every 12 weeks, as applicable (see exclusion criteria, protocol Section 4.3).
o
Subjects previously treated for latent TB (see Inclusion # 9) do not need to have the QuantiFERON® TB-Gold In-Tube test (or equivalent assay), but a chest radiograph must 
be obtained if one is not available within 3 months prior to screening (with the report or films available for investigator review). All other subjects must have the 
QuantiFERON® TB-Gold In-Tube test (or equivalent assay) at screening and a chest radiograph (views as per local guidelines) at screening or within 3 months prior to 
screening (with the report or films available for investigator review).
p
Pharmacokinetic samples will be collected on Week 2 (at least 30 minutes and up to 3 hours after dosing), Week 4 (anytime), Week 12 (within 2 hours prior to study drug 
administration), and Week 24 (within 2 hours prior to study drug administration).
 
.
s
On Day 1, biomarker samples will be collected prior to study drug administration.
t
At the end of the Week 12 visit, subjects on placebo will be re-randomized 1:1 in a blinded fashion to receive filgotinib 200 mg + PTM GS-9876 30 mg once daily or 
GS-9876 30 mg + PTM filgotinib 200 mg once daily for the remainder of the study.
u
For subjects who enter the 24-week extension period only.
v
See protocol Section 6.9.2.3 for details.
w
A separate manual will be provided for instructions on photography of areas with skin involvement.
x
See protocol Section 6.9.2.4 for details.
y
To be performed at ET visit if not completed within the prior 12 weeks
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Filgotinib and Lanraplenib
Statistical Analysis Plan
GS-US-436-4092
Version 1.0
CONFIDENTIAL
Page 50
12 May 2019
Appendix 2.
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
(CLASI)
E 
X 
e 
n 
Sel.ect the soore in eacll anatomical l'.ocation tllatl:lescrfbes tlle most seve.rely affected cutaneous l'upus.associ,ated 1:e.siorn 
A ·1omical l ocation 
Sc.alp 
tif5 
No.se (in.cl ma:la:r area) 
ResJ of the face 
Post. Nect & /or sho11l<P..IS 
i',bdomen 
S.adk.. buttoclks 
li.rm:s 
Legs 
F,e,et 
Mucous membrarne 
0-absent 
1-!le:siion 01 ube.ra · n 
Al'opecia 
Recen.t Hair loss 
activity 
0-absent 
1-pi 
; faint eiytli.Emi> 
2- ,ed; 
=~ 
red; 
purple /viola:oeous / 
c:rasted / lt""1ormagic 
0-absent; 
1•seale 
2-vemtoous I 
hype,trophic 
• ·1 3>ll days /a;; reported by p.s.ti2 
1-Y,es 
o..No 
damage 
Oyspjg;mentation 
0--.s.bs~ !, 
1-dysp\gmentaton 
Dyspigmentation 
=
r,mg / 
Allojilly/ 
Panni<>tlfitis 
0 .•. absent 
1 ... ·seamr,g 
2 ... severely 
.allophic s=rrir,g 
or • 
· ulitis 
A ·tomical ooation 
Scalp 
Ears 
Nose (me!. m.ala:r a:rea) 
R,est of the face 
Post. Necl<. &/or shoul<t= 
Chest 
A!>:1,omen 
S.ac\;. btrl1oo\s 
Arms 
Report dwa · 
· -- · 
-
p.· 
-
• 
- -
-
- e:I 
{\lelio.a.1 fe;p0 
Oyspigm • 
a1ion 
-score above rema:iru) 
Oys~m 
·lion 11Sually la6ts at least 12 mooths (dysp\;Jmentation 
scor,e ·· do led) 
NB: if scarring andnon--5Ca1I"ing aspects saem 
to co;e.x.ist in onel.e-sioD: please sco:re both 
Oiville tihe scalp · to four q • • ts a;; shown. The div" 
l>!atween · t and kaft is the midlillle. The divicm;I iin,, betw0"Jl f,on ·• and oooil>Ml 
is llt'e line ooJIJleOtin,g lhe · l>est points of the ea:r lote. A qua!!ra 1 is ooasict'efed affected · !here is a kasion wiitihin lhe qu.a-11· 
Alopecia (clinically oot obviou,;!ly scarred) 
0-absP 1 
1-<fmfuse; oo.n-i 
- m mato.ry 
2-fooa1 or p.s.tcl,y in or,e q ·dran , 
3--focal or p.s.tcl,y in more than one q ·mant 
Total Aotivity Score 
(Fci:r the ;::or.i\,; ty SC<lfl:! !Jl]eii':! 2.'dd n.p tihe :iOIJre:5 
of the ],;ft ,ide i _ for E,;,1lLeim, &ale I Hyp-ophy. 
Muoous n:an:bruie invalven:=IJ.t .me! Alapecia) 
Sca.lilir,g of lihe scalp {joojj;ed climca1!y) 
&- absent 
3- io o.neq - ra t 
4- two qua,!!ra:nts 
5- ' "" 
• • 1s 
6- affects lihe whole s , 
Total Dama§a Score 
(F<11 m i: ciam::.5= :;core. ple:.5e: 2.dd n.p :tih i: :;aire:5 
of tih':! ri~ t side. 1 _ for Dyspi~ ~ t:.ti<Jll,, 
Scamn,g .rA!Japhy• !>-oJllllmliti; .me! ScamI\f. 
of the &alp)