Conditions: Lupus Membranous Nephropathy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 9
Healthy volunteers: no

Brief summary:
The primary objective of this study is to evaluate the efficacy of filgotinib and lanraplenib (previously GS-9876) in adults with lupus membranous nephropathy (LMN).

Detailed description:

Arms:
arm 1: Participants receive lanraplenib 30 mg tablet + filgotinib placebo tablet orally once daily for 16 weeks in Blinded Treatment Phase. Participants who achieve ≥ 35% reduction in urinary protein excretion from baseline continue to receive same blinded study treatment for additional 16 weeks. Participants who did not achieve a ≥ 35% reduction in urinary protein excretion will switch treatment.

After 32 weeks of blinded treatment, participants who have ≥ 35% reduction in urinary protein excretion from baseline continue their assigned blinded treatment for additional 20 weeks in Extended Blinded Treatment Phase. arm 2: Participants receive filgotinib 200 mg tablet + lanraplenib placebo tablet orally once daily for 16 weeks in Blinded Treatment Phase. Participants who achieve ≥ 35% reduction in urinary protein excretion from baseline continue to receive same blinded study treatment for additional 16 weeks. Participants who did not achieve a ≥ 35% reduction in urinary protein excretion will switch treatment.

After 32 weeks of blinded treatment, participants who have ≥ 35% reduction in urinary protein excretion from baseline continue their assigned blinded treatment for additional 20 weeks in Extended Blinded Treatment Phase. arm 3: At Week 16, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from baseline to Week 16 switch treatment and receive filgotinib 200 mg + lanraplenib placebo for additional 16 weeks.

At Week 32, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from Week 16 to Week 32 can continue whichever treatment that lead to the greatest reduction in urinary protein excretion, or either treatment per investigator's discretion for additional 20 weeks in Extended Blinded Treatment Phase. arm 4: At Week 16, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from baseline to Week 16 switch treatment and receive lanraplenib 30 mg + filgotinib placebo for additional 16 weeks.

At Week 32, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from Week 16 to Week 32 can continue whichever treatment that lead to the greatest reduction in urinary protein excretion, or either treatment per investigator's discretion for additional 20 weeks in Extended Blinded Treatment Phase.

Interventions: intervention 1: Filgotinib intervention 2: Lanraplenib intervention 3: Filgotinib placebo intervention 4: Lanraplenib placebo
Intervention descriptions: intervention 1: 200 mg tablet administered orally once daily intervention 2: 30 mg tablet administered orally once daily intervention 3: Tablet administered orally once daily intervention 4: Tablet administered orally once daily

Protocol document:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 2, Randomized, Double-Blind, Multicenter Study Evaluating the 
Safety and Efficacy of Filgotinib and GS-9876 in Subjects with Lupus 
Membranous Nephropathy (LMN)
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
123903
EudraCT Number:
Not Applicable
Clinical Trials.gov 
Identifier:
NCT03285711
Indication:
Lupus Membranous Nephropathy
Protocol ID:
GS-US-437-4093
Gilead Clinical Program 
Manager:
Name:
Telephone:
Fax:
Email:
Gilead Medical Monitor:
Name:
Telephone:
Fax:
Mobile:
Email:
Protocol Version/Date:
Original:
09 March 2017
Amendment 1:
05 July 2017
Amendment 2:
21 March 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
PPD
PPD
PPD
PPD
PPD
PPD
(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....................................................................18
1.
INTRODUCTION ..............................................................................................................................................21
1.1.
Background ............................................................................................................................................21
1.2.
Filgotinib................................................................................................................................................23
1.2.1.
General Information .............................................................................................................23
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................23
1.2.3.
Clinical Trials of Filgotinib..................................................................................................24
1.3.
GS-9876 .................................................................................................................................................24
1.3.1.
Nonclinical Pharmacology and Toxicology .........................................................................24
1.3.2.
Clinical Trials of GS-9876 ...................................................................................................27
1.4.
Rationale for This Study ........................................................................................................................28
1.4.1.
Rationale for Endpoint and Timing......................................................................................29
1.4.2.
Rationale for Dose................................................................................................................29
1.5.
Risk/Benefit Assessment for the Study..................................................................................................30
1.6.
Compliance ............................................................................................................................................31
2.
OBJECTIVES.....................................................................................................................................................32
3.
STUDY DESIGN................................................................................................................................................33
3.1.
Endpoints ...............................................................................................................................................33
3.2.
Study Design..........................................................................................................................................34
3.3.
Study Treatments ...................................................................................................................................35
3.4.
Duration of Treatment............................................................................................................................36
3.5.
Discontinuation Criteria.........................................................................................................................36
3.5.1.
Study Drug Interruption Considerations...............................................................................36
3.5.2.
Study Drug Discontinuation Criteria....................................................................................37
3.6.
End of Study...........................................................................................................................................39
3.7.
Post Study Care......................................................................................................................................39
3.8.
Biomarker Testing..................................................................................................................................39
3.8.1.
Biomarker Samples to Address the Study Objectives ..........................................................39
4.
SUBJECT POPULATION..................................................................................................................................42
4.1.
Number of Subjects and Subject Selection ............................................................................................42
4.2.
Inclusion Criteria....................................................................................................................................42
4.3.
Exclusion Criteria...................................................................................................................................44
4.4.
Screen Failures.......................................................................................................................................47
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................48
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................48
5.1.1.
Procedures for Breaking Treatment Codes...........................................................................48
5.2.
Description and Handling of GS-9876, PTM GS-9876, Filgotinib and PTM Filgotinib .......................48
5.2.1.
Formulation of GS-9876 and PTM GS-9876 .......................................................................48
5.2.2.
Formulation of Filgotinib and PTM Filgotinib.....................................................................49
5.2.3.
Packaging and Labeling of Study Drugs..............................................................................49
5.2.4.
Storage and Handling of Study Drugs..................................................................................49


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5.2.5.
Dosage and Administration of GS-9876 ..............................................................................50
5.2.6.
Dosage and Administration of Filgotinib .............................................................................50
5.3.
Prior and Concomitant Medications.......................................................................................................50
5.3.1.
Allowed Concomitant Medications......................................................................................51
5.3.2.
Prohibited Concomitant Medications...................................................................................52
5.4.
Vaccine Guidelines ................................................................................................................................54
5.5.
Accountability for Study Drugs .............................................................................................................54
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................54
6.
STUDY PROCEDURES ....................................................................................................................................55
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................55
6.2.
Pretreatment Assessments......................................................................................................................55
6.2.1.
Screening Visit .....................................................................................................................55
6.2.2.
Day 1 Baseline Assessments ................................................................................................57
6.3.
Randomization .......................................................................................................................................59
6.4.
Week 1 Assessments..............................................................................................................................59
6.5.
Weeks 2 through Week 28 Assessments (excluding Week 16) .............................................................59
6.6.
Week 16 and Week 32 Assessments ......................................................................................................60
6.7.
Week 36 through Week 48 Assessments................................................................................................62
6.8.
Week 52 Assessments............................................................................................................................63
6.9.
Early Termination Assessments.............................................................................................................64
6.10.
Final Follow-Up Assessments (4 Weeks Post Treatment) .....................................................................65
6.11.
Unscheduled Visit (exacerbation of LMN)............................................................................................66
6.12.
Study Assessments.................................................................................................................................66
6.12.1.
Priority of Assessments........................................................................................................66
6.12.2.
Efficacy ................................................................................................................................66
6.12.3.
Safety....................................................................................................................................68
6.12.4.
Clinical Laboratory Evaluations...........................................................................................68
6.12.5.
Vital Signs............................................................................................................................68
6.12.6.
Physical Examination...........................................................................................................68
6.12.7.
Other Safety Assessments ....................................................................................................69
6.13.
Pharmacokinetics Assessments..............................................................................................................69
6.14.
Biomarker Assessments .........................................................................................................................69
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................70
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................70
7.1.1.
Adverse Events.....................................................................................................................70
7.1.2.
Serious Adverse Events........................................................................................................70
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................71
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................71
7.2.2.
Assessment of Severity ........................................................................................................72
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................72
7.4.
Gilead Reporting Requirements.............................................................................................................74
7.5.
Clinical Laboratory Abnormalities.........................................................................................................74
7.6.
Toxicity Management ............................................................................................................................75
7.6.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................75
7.6.2.
Grades 3 Laboratory Abnormality or Clinical Event ...........................................................75
7.6.3.
Grades 4 Laboratory Abnormality or Clinical Event ...........................................................75
7.7.
Special Situations Reports......................................................................................................................76
7.7.1.
Definitions of Special Situations..........................................................................................76
7.7.2.
Instructions for Reporting Special Situations.......................................................................77
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8.
STATISTICAL CONSIDERATIONS................................................................................................................79
8.1.
Analysis Objectives and Endpoints........................................................................................................79
8.1.1.
Analysis Objectives..............................................................................................................79
8.1.2.
Primary Endpoint .................................................................................................................79
8.1.3.
Secondary Endpoints............................................................................................................79
8.1.4.
Exploratory Endpoints..........................................................................................................80
8.1.5.
Biomarker Endpoints............................................................................................................81
8.2.
Analysis Conventions.............................................................................................................................81
8.2.1.
Analysis Sets ........................................................................................................................81
8.3.
Data Handling Conventions ...................................................................................................................82
8.4.
Demographic Data and Baseline Characteristics ...................................................................................82
8.5.
Efficacy Analysis ...................................................................................................................................82
8.5.1.
Primary Analysis..................................................................................................................82
8.5.2.
Secondary Analyses .............................................................................................................82
8.5.3.
Exploratory Analyses ...........................................................................................................83
8.6.
Safety Analysis.......................................................................................................................................83
8.6.1.
Extent of Exposure...............................................................................................................83
8.6.2.
Adverse Events.....................................................................................................................83
8.6.3.
Laboratory Evaluations ........................................................................................................84
8.6.4.
Other Safety Evaluations......................................................................................................84
8.7.
Pharmacokinetic Analysis......................................................................................................................84
8.8.
Biomarker Analysis................................................................................................................................84
8.9.
Sample Size............................................................................................................................................85
8.10.
Data Monitoring Committee ..................................................................................................................85
8.11.
Analysis Schedule ..................................................................................................................................85
9.
RESPONSIBILITIES..........................................................................................................................................86
9.1.
Investigator Responsibilities ..................................................................................................................86
9.1.1.
Good Clinical Practice..........................................................................................................86
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................86
9.1.3.
Informed Consent.................................................................................................................86
9.1.4.
Confidentiality......................................................................................................................87
9.1.5.
Study Files and Retention of Records ..................................................................................87
9.1.6.
Case Report Forms...............................................................................................................88
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................89
9.1.8.
Inspections............................................................................................................................89
9.1.9.
Protocol Compliance............................................................................................................89
9.2.
Sponsor Responsibilities ........................................................................................................................90
9.2.1.
Protocol Modifications.........................................................................................................90
9.2.2.
Study Report and Publications .............................................................................................90
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................90
9.3.1.
Payment Reporting...............................................................................................................90
9.3.2.
Access to Information for Monitoring..................................................................................91
9.3.3.
Access to Information for Auditing or Inspections ..............................................................91
9.3.4.
Study Discontinuation..........................................................................................................91
10.
REFERENCES ...................................................................................................................................................92
11.
APPENDICES ....................................................................................................................................................97
Appendix 1.
Investigator Signature Page....................................................................................................98
Appendix 2.
Study Procedures Table..........................................................................................................99
Appendix 3.
Management of Clinical and Laboratory Adverse Events....................................................104


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Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) v4.03..................................105
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................106
Appendix 6.
Clinical Laboratory Assessment Table.................................................................................110
Appendix 7.
Safety of Estrogens in Lupus Erythematosus National Assessment trial-based 
Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) ....................111
Appendix 8.
British Isles Lupus Activity Group (BILAG) Index.............................................................112
Appendix 9.
Physician’s Global Assessment of Disease Activity ............................................................113
Appendix 10.
Patient Global Assessment of Disease Activity....................................................................114
Appendix 11.
36-Item Short Form Health Survey ......................................................................................115
LIST OF IN-TEXT TABLES
Table 1-1.
Margins for GS-9876 Based on Systemic Exposure Relative to the Observed 
Human Exposure at 30 mg once daily (AUC)........................................................................26
Table 5-1.
Prohibited Medications...........................................................................................................52
Table 7-1.
Grading of Adverse Event Severity........................................................................................72
LIST OF IN-TEXT FIGURES
Figure 3-1.
Study Schema.........................................................................................................................35


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title:
A Phase 2, Randomized, Double-Blind, Multicenter Study Evaluating 
the Safety and Efficacy of Filgotinib and GS-9876 in Subjects with 
Lupus Membranous Nephropathy (LMN)
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
123903
Not Applicable
NCT03285711
Study Centers 
Planned:
Approximately 20 centers in North America
Objectives:
The primary objective of this study is:

To evaluate the efficacy of filgotinib and GS-9876 in subjects 
with LMN
The secondary objectives of this study are: 

To evaluate the safety and tolerability of filgotinib and GS-9876 
in subjects with LMN

To evaluate the pharmacokinetics (PK) of filgotinib and GS-9876 
in subjects with LMN
The exploratory objectives of this study are:
 
 
 
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Study Design:
This is a Phase 2, randomized, double-blind, multicenter study in 
subjects with LMN. Subjects will be randomized in a 1:1 ratio to 
receive once daily oral doses of the following study drugs for 
16 weeks:
Arm
Study Drugs
Filgotinib (n=16)
Filgotinib 200 mg + PTM GS-9876
GS-9876 (n=16)
GS-9876 30 mg + PTM Filgotinib
PTM = Placebo to match
Randomization will be stratified by prior treatment with 
cyclophosphamide. 
Urinary protein excretion will be determined using 2 methods – two 
consecutive morning voids as well as a 24-hour urine collection. For 
the Baseline (Day 1) assessment, all 3 urine samples will be collected 
prior to Day 1, with the 24-hour urine collection as close to the Day 1 
visit as possible. At Week 16, the primary study endpoint will be 
assessed by urine protein excretion during a 24-hour urine collection.
Two consecutive morning voids prior to the Week 16 visit will be 
used to determine response for subsequent study treatment. All 
subjects who achieve a ≥ 35% reduction in urinary protein excretion 
(using an average of the urine protein creatinine ratio [UPCR] from 
2 morning voids) from Baseline (Day 1) will continue to receive their 
assigned blinded study treatment (filgotinib 200 mg + PTM 
GS-9876, or GS-9876 30 mg + PTM filgotinib) for an additional 
16 weeks. Additional details regarding urine collection procedures 
will be specified in the Laboratory Manual and Subject Procedures 
Manual.
Subjects who do not achieve a ≥ 35% reduction in urinary protein 
excretion from Baseline (Day 1) to Week 16 will switch study 
treatment for 16 weeks in a blinded fashion (ie, those on filgotinib 
will switch to GS-9876 + PTM filgotinib, while those on GS-9876 
will switch to filgotinib + PTM GS-9876). 
After 32 weeks of blinded treatment, those who have 
a ≥35% reduction in urinary protein excretion (using an average of 
the UPCR from 2 morning voids) from Day 1 (for subjects who 
remained on the randomized study treatment after Week 16) or from 
Week 16 (for subjects who switched treatment at Week 16) will 
continue their assigned blinded treatment for an additional 20 weeks 
in the Extended Blinded Treatment Phase.  


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Subjects that do not achieve a ≥ 35% reduction in urinary protein 
excretion from Day 1 (for subjects who remained on the randomized 
study treatment after Week 16) or from Week 16 (for subjects who 
switched treatment at Week 16) to Week 32 will be allowed to 
continue whichever study treatment led to the greatest reduction in 
urinary protein excretion (from Day 1 to Week 16 on initial study 
treatment or from Week 16 to Week 32 on switched treatment), or 
either study treatment per the Investigator’s discretion (eg, 
differences in tolerability or other non-renal benefits that support 
overriding the treatment assignment according to reduction in urinary 
protein excretion) during the Extended Blinded Treatment Phase.
All subjects, including those who terminate early from the study, will 
be required to complete a Final Follow-Up (FU) visit 4 weeks 
(± 5 days) after the last dose of study drug.
RANDOMIZATION 
1:1 
(N=32) 
DAYl 
Baseline 
Blinded Treatment Phase 
WK16 
1° Endpoint 
WK32 
Extended Blinded 
Treatment Phase 
Filgotinib200 mg+ 
PTM GS-9876 
GS-9876 30 mg + 
PTM Filgotinib 
GS-9876 30 mg+ 
PTM Filgotinib 
GS-9876 30 mg + 
PTM Filgotinib 
Filgotinib200 mg+ 
PTMGS-9876 
' 
T 
'f 
WK 16: Subjects w ith a ~ 3556 reduction in 
WK 32: SubjecGwith a ~ 35% reduction in urinary 
urin ary proteinexaetion fromSas.eline (Day 1) 
protein exretion from Day l (for subjects w ho 
to Week 16wilt continue to receive their 
rem ai ned on the randomized srudy traatmentaftar 
assigned blinded study treatment for an 
Wee k 16)orfrom Week 16{forsubjects who 
additional l6weeks. 
switched t'fl!atment at W eek 16)w illcontinueto 
Subjectsth atdo notadiiew a ~ 3556 redur::tion 
receivetheirassigned blinded study treatmentfor 
in urinary protein e,x:retioo w ill switch study 
an additional20weelts. 
Subjectsthatdo not achiew a~ 35% reduction in 
urin ary pratein e xcretion from Day 1 {for subjects 
who remained on the randomized study treatment 
after Week 16} orfrom Week 16{for sl.b,iect.swho 
switched treatment at Week 16)toWe ek 32 c:1n 
continuewhidlever treatment led to the gre3test 
red uction in urinary proteinexueticm (from Day 1 
to Week 16on initial .studytreatmentorfrom 
Week 16 to We ek 32 on switdied traatment), o r 
either stuOftreatment per the lnve,,"tig:1tor's 
discretion. 
WK52 WK56 
Follow-Up 


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Substudies:
 
 
 
 
 
 
 
 
 
 
Number of Subjects 
Planned:
Approximately 32 subjects
Target Population:
Male or female subjects between 18 and 75 years of age, inclusive,
with active lupus membranous nephropathy who are not in partial or 
complete remission in response to treatment with one or more 
anti-inflammatory or immunosuppressive agents.
Duration of 
Treatment:
Subjects will receive a maximum of 52 weeks of study drug(s).
Diagnosis and Main 
Eligibility Criteria:
For a complete list of study inclusion and exclusion criteria, 
please refer to Section 4.
Key Inclusion Criteria
1) Male or female between 18 and 75 years of age, inclusive, at the 
time of initial informed consent
2) Kidney biopsy within the 36 months prior to Screening with a 
histologic diagnosis of LMN (International Society of 
Nephrology [ISN] and the Renal Pathology Society [RPS] 2003 
classification of lupus nephritis), either Class V alone, or Class V 
in combination with Class II. If the biopsy indicates segmental 
glomerular scarring indicative of prior Class III or IV lesions but 
there is limited or no evidence of current Class III or IV activity, 
the subject would be eligible if the Class V findings are active. 
A copy of the kidney biopsy pathology report will be obtained 
from each subject and forwarded to the Gilead Medical Monitor 
for review and confirmation of eligibility prior to randomization 
on Day 1.
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3) Urine protein excretion  ≥ 1.5 grams per day based on 24-hour 
urine sample collected during Screening 
4) Estimated glomerular filtration rate (eGFRMDRD) 
≥40 mL/min/1.73 m2 based on the MDRD formulation at 
Screening 
5) Prior treatment for LMN with at least one immunosuppressive 
therapy for a sufficient duration before Screening, including but 
not limited to:
a) Calcineurin inhibitors (cyclosporin A, tacrolimus),
b) Alkylating agents (chlorambucil, cyclophosphamide), or
c) Antimetabolite drugs (azathioprine, mycophenolate mofetil) 
d) Other (eg, methotrexate, leflunomide, moderate- to high-dose 
steroids, etc.)
Prior therapy should be specified on the Prior and Concomitant 
Medication – LMN and SLE eCRF (ie, therapy name, dose, and 
start/stop dates).
6) Treatment with an angiotensin-converting enzyme inhibitor 
(ACEi) or angiotensin II receptor blocker (ARB) at a dose 
deemed appropriate for the subject per the Investigator for at least 
6 weeks prior to and during Screening, with a stably prescribed 
dose for at least 14 days prior to Day 1. Enrolled subjects should 
remain on the stably prescribed dose of ACEi or ARB treatment 
throughout the study.
Subjects who are not taking any ACEi or ARB may be screened 
if there is documented intolerance to ACEi and/or ARB.  
7) If a subject is taking oral glucocorticoids, the dose must be 
≤20 mg/day prednisone (or equivalent) and must have been on a 
stably prescribed dose for at least 28 days prior to Day 1. Enrolled 
subjects should remain on the stably prescribed dose of 
prednisone treatment through Week 16 of the study (after 
assessment of the primary outcome). 
8) If a subject is taking the following agents, they must have been on 
a stably prescribed dose for at least 28 days prior to Day 1: 
a) Hydroxychloroquine (≤400 mg/day),
b) Chloroquine (≤ 250 mg/day), or 
c) Quinacrine (≤ 100 mg/day)
Enrolled subjects should remain on the stably prescribed dose of 
the above treatments throughout the study.  


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9) Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is 
permitted if the dose has been stably prescribed for at least 
14 days prior to Day 1. Enrolled subjects should remain on the 
stably prescribed dose of NSAID treatment throughout the study. 
Intermittent use (pro re nata [PRN]) for non-LMN indications 
should be minimized.
10) All disease modifying anti-rheumatic drugs (DMARDs) or 
immunosuppressive agents other than glucocorticoids, 
hydroxychloroquine (as specified above), azathioprine (up to a 
maximum of 2 mg/kg body weight/day or 200 mg/day, whichever 
is lower), and methotrexate (≤ 20 mg per week) should be 
withdrawn at least 28 days prior to Day 1.
11) Systolic blood pressure (SBP) below 160 mmHg AND diastolic 
blood pressure (DBP) below 90 mmHg will be measured at 
Screening. The Screening blood pressure may be repeated 
(a maximum of 2 times) as an unscheduled visit prior to Day 1.
12) Meet the following tuberculosis (TB) Screening criteria: 
a) No evidence of active or latent TB as assessed during 
Screening by:

A negative QuantiFERON® TB-Gold In-Tube test at 
Screening AND

A chest radiograph (if consistent with local guidelines) 
taken at Screening or within 90 days prior to Screening 
(with the report or films available for Investigator review) 
without evidence of active or latent TB infection 
b) Subjects previously treated for latent TB: subject who has 
previously received an adequate course of therapy as per local 
standard of care for latent TB (eg, 9 months of isoniazid in a 
location where rates of primary multi-drug resistant TB 
infections are <5% or an acceptable alternative regimen). In 
these cases, no QuantiFERON® TB-Gold In-Tube test 
(or equivalent assay) need be obtained, but a chest radiograph 
must be obtained if not done so within 90 days prior to 
Screening (with the report or films available for Investigator 
review). It is the responsibility of the Investigator to verify 
the adequacy of previous anti-tuberculosis treatment and 
provide appropriate documentation. Subjects with a history of 
untreated or inadequately treated latent TB are excluded from 
the study
c) Subjects with newly identified latent TB during Screening are 
excluded from the study.  


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Cases falling under category “b” need to be approved by the 
Sponsor prior to enrollment in the study. Subjects with any 
history of or current active TB (regardless of past or present 
anti-TB treatment) are excluded.
Key Exclusion Criteria
1) Prior treatments as follows:
a) Previous treatment with a JAK inhibitor within 3 months of 
Day 1
b) Use of rituximab or other selective B lymphocyte depleting 
agents (including experimental agents) within 6 months of 
Day 1. Enrollment is permitted if the last dose was given 
> 6 months and CD19-positive B cells are detectable at 
Screening.
c) Anticipated use of disallowed medications in Section 5.3.2
2) Known hypersensitivity or allergy to the study drugs 
(filgotinib, GS-9876), their metabolites, or formulation excipients
3) History of, or current, inflammatory or autoimmune disease other 
than SLE (e.g., scleroderma, reactive arthritis, rheumatoid 
arthritis, ankylosing spondylitis, Lyme disease) that will interfere 
with clinical evaluation during the study, per judgment of the 
Investigator. Secondary Sjogren’s syndrome or controlled 
thyroiditis is acceptable, per judgment of the Investigator.
4) Administration of a live/attenuated vaccine within 30 days prior 
to Day 1, or planned during the study or through 12 weeks after 
subject’s last dose of study drug
Study Procedures/
Frequency:
After the screening period and randomization on Day 1, eligible 
subjects will enter the Blinded Treatment Phase and return to the 
study center at specified visits.
Blinded Treatment Phase

Weeks 1, 2, 4, 8, 12, 16, 18, 20, 24, 28, and 32 
Following completion of 16 weeks of dosing, the primary endpoint of 
the study will be evaluated in all subjects. To test their change in 
urinary protein excretion, subjects will submit 2 consecutive morning 
urine void samples to the study center approximately 7 days prior to 
the Week 16 visit. These results will inform their treatment 
assignment for the additional 16 weeks. Subjects who achieve a 
≥35% reduction in urinary protein excretion (using an average of the 
UPCR from 2 morning voids) from Baseline (Day 1) to Week 16 will 
continue to receive their assigned blinded study treatment (filgotinib 


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200 mg + PTM GS-9876 once daily; or GS-9876 30 mg + PTM 
filgotinib once daily) for an additional 16 weeks. Those subjects who 
do not achieve a ≥35% reduction in urinary protein excretion from 
Baseline (Day 1) to Week 16 will switch study treatment for 16 
weeks in a blinded fashion (ie, those on filgotinib 200 mg + PTM 
GS-9876 once daily will switch to GS-9876 30 mg + PTM filgotinib 
once daily, while those on GS-9876 30 mg + PTM filgotinib 200 mg 
once daily will switch to filgotinib 200 mg + PTM GS-9876 once 
daily). The primary outcome for urinary protein excretion will be 
determined using a 24-hour urine collection that is collected 
immediately prior to the Week 16 visit, or as close to the Week 16 
visit as possible. Additional details regarding urine collection 
procedures will be specified in the Laboratory Manual and Subject 
Procedures Manual.
After 32 weeks of blinded treatment, those who have received some 
benefit (a ≥ 35 % reduction in urinary protein excretion using an 
average of the UPCR from 2 morning voids from Day 1 [for subjects 
who remained on the randomized study treatment after Week 16] or 
from Week 16 [for subjects who switched treatment at Week 16]) 
will continue on their assigned blinded treatment for an additional 
20 weeks in the Extended Blinded Treatment Phase. To test their 
change in urinary protein excretion, subjects will submit 
2 consecutive morning urine void samples to the study center 
approximately 7 days prior to the Week 32 visit. These results will 
inform their treatment assignment for the additional 20 weeks in the 
Extended Blinded Treatment Phase. Subjects will also submit a 
24-hour urine collection that is collected immediately prior to the 
Week 32 visit, or as close to the Week 32 visit as possible. Subjects 
who do not achieve a ≥35% reduction in urinary protein excretion 
from Day 1 (for subjects who remained on the randomized study 
treatment after Week 16) or from Week 16 (for subjects who 
switched treatment at Week 16) to Week 32 will be allowed to 
continue whichever study treatment led to the greatest reduction in 
urinary protein excretion (from Day 1 to Week 16 on initial study 
treatment or from Week 16 to Week 32 on switched treatment), or 
either study treatment per the Investigator’s discretion 
(eg, differences in tolerability or other non-renal benefits that support 
overriding the treatment assignment according to reduction in urinary 
protein excretion) during the Extended Blinded Treatment Phase. 
Extended Blinded Treatment Phase

Weeks 36, 40, 44, 48, and 52 
All subjects who received at least one dose of study drug and 
discontinue the study early will complete an Early Termination (ET) 
visit at the time of study discontinuation. 


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All subjects, including those who terminate early from the study, will 
be required to complete a Final Follow-Up (FU) visit 4 weeks 
(± 5 days) after the last dose of study drug. For subjects that complete 
the entire study, the Final FU visit will be conducted at Week 56.
Screening Study Assessments:
Complete medical history, complete physical exam (PE) 
(including height and weight), morning urine voids and 24-hour urine 
collection for protein, urinalysis (with urine microscopy and spot 
protein-to-creatinine ratio), vital signs (ie, blood pressure, respiratory 
rate, heart rate, and body temperature), clinical laboratory tests 
(hematology, serum chemistry, and coagulation), hemoglobin A1c 
(HbA1c), thyroid stimulating hormone (TSH) test, C-reactive protein 
(CRP), erythrocyte sedimentation rate (ESR), autoantibody panel and 
complement levels, serum pregnancy test for females of childbearing 
potential or follicle stimulating hormone (FSH) test for females of 
nonchildbearing potential (as defined in Appendix 5), human 
immunodeficiency virus type 1 and 2 (HIV-1, HIV-2) test, 
hepatitis B virus (HBV) tests, hepatitis C virus (HCV) test, HCV 
RNA monitoring (if subject is HCV Ab positive), QuantiFERON®
TB-Gold In-Tube Test (if applicable) and chest x-ray (if one has not 
already been obtained within 3 months prior to screening), and 
standard 12-lead electrocardiogram (ECG).
Subjects will be screened up to 35 days prior to randomization 
(Day 1) to determine eligibility for participation in the study. The 
Screening visit will take two separate days to complete.  In addition, 
Screening Day 2 cannot occur earlier than 3 days after Screening 
Day 1 due to the timing of the morning urine voids and the 24 hour 
urine collection.  Additional details regarding urine collection 
procedures will be specified in the Laboratory Manual and Subject 
Procedures Manual.
Day 1 (Baseline) through Final Follow-Up Visit Assessments:
At a minimum, the following safety assessments will be performed at 
every study visit (refer to Appendix 2 for a complete list of required 
study assessments for each study visit):
Urinalysis (with urine microscopy and spot protein-to-creatinine 
ratio) (except Final FU visit), vital signs (ie, blood pressure, 
respiratory rate, heart rate, and body temperature), clinical laboratory 
tests (hematology, serum chemistry, and coagulation), CRP, ESR, 
HCV RNA monitoring (if applicable) and urine pregnancy test for 
females of childbearing potential.


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Complete PE, symptom-driven PE, weight, morning urine voids and 
24-hour urine collection for protein, fasting lipids, quantitative serum 
immunoglobulin test, autoantibody panel and complement levels, 
Safety of Estrogens in Lupus Erythematosus National Assessment 
trial-based SLE Disease Activity Index (SELENA-SLEDAI), 
British Isles Lupus Activity Group (BILAG) Index, Patient Global 
Assessment of Disease Activity, Physician’s Global Assessment of 
Disease Activity, 36-Item Short Form Health Survey, 
standard 12-lead ECG, in-clinic study drug administration, study 
drug accountability, and study drug dispensation will be performed at 
selected study visits (refer to Appendix 2).  
Early Termination Study Assessments:
Complete PE, weight, vital signs (ie, blood pressure, respiratory rate, 
heart rate, and body temperature), clinical laboratory tests 
(hematology, serum chemistry, and coagulation), CRP, ESR, HCV 
RNA monitoring (if applicable), urine pregnancy test for females of 
childbearing potential, standard 12-lead ECG, and study drug 
accountability.
Assessment of adverse events (AEs) and concomitant medications 
will continue throughout the duration of the study.
Pharmacokinetic (PK) Assessments:
Blood samples will be collected for plasma PK analysis of filgotinib 
and its active metabolite GS-829845, and GS-9876 post dose at 
Weeks 2, 4 and 20 (at least 30 minutes and up to 3 hours after 
dosing), anytime at Weeks 8 and 24, and within 2 hours prior to 
dosing at Weeks 16 and 32.
Urine PK analyses may be performed for filgotinib and its active 
metabolite GS-829845, and GS-9876, using the 24-hour urine 
collection at Week 16.
Biomarker Assessments:
Urine samples will be collected for biomarker assessments at 
Screening, Day 1 (predose), Weeks 2, 16, 32, 52, ET, and at the Final 
FU.  
Blood samples for biomarker assessments (whole blood TBNK 
biomarker, serum and plasma biomarkers, vfPBMC, and PAXgene 
RNA) will be collected at Screening, Day 1 (predose), Weeks 2, 16, 
32, 52, ET, and at the Final FU.  
Concomitant Medication Management:
Stable medications at Day 1 (per Section 5.3.1) are to be continued 
during the study. Refer to Table 5-1 for a list of prohibited 
medications.


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Test Product, Dose, 
and Mode of 
Administration:
Filgotinib 200 mg (1 200 mg tablet) administered orally once daily 
in the AM
GS-9876 30 mg (1 30 mg tablet) administered orally once daily in 
the AM
Reference Therapy, 
Dose, and Mode of 
Administration:
PTM Filgotinib (1 tablet) administered orally once daily in the AM
PTM GS-9876 (1 tablet) administered orally once daily in the AM
Criteria for 
Evaluation:
Safety:
Safety will be assessed during the study through the reporting of 
AEs, clinical laboratory tests, vital sign assessments, physical 
examinations findings, and ECGs. Treatment emergent AEs 
including infection, worsening of proteinuria, or decrease in eGFR 
will be of particular interest.   
Efficacy:
Primary Endpoint

The percent change in urine protein from Baseline (Day 1) to 
Week 16 (assessed by urine protein excretion during a 24-hour 
urine collection). 
Secondary Endpoints

Change from Baseline (Day 1) in urine protein (assessed by urine 
protein excretion during a 24-hour urine collection) at Week 16 

Change from Baseline (Day 1) in eGFR at Week 16

Change from Baseline (Day 1) in UPCR (assessed by urine 
protein excretion during a 24-hour urine collection) at Week 16

Proportion of subjects with partial remission (defined as urine 
protein excretion below < 3 g/d and urine protein excretion 
decrease by ≥ 50% among subjects with Baseline (Day 1) 
nephrotic range proteinuria [urine protein excretion ≥3 g/d]; or 
urine protein excretion decrease by ≥ 50% among subjects with 
subnephrotic range proteinuria [urine protein excretion < 3 g/d]) 
at Week 16

Proportion of subjects with complete remission (defined as urine 
protein excretion below 0.5 g/day, with no hematuria) at Week 16
Biomarker Endpoints

Change in JAK-STAT-, SYK-, and disease-related biomarkers in 
peripheral blood and urine


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
Association of changes in peripheral blood and urine biomarkers 
with clinical outcomes

Association of Baseline markers with disease severity and 
response to filgotinib and GS-9876
Pharmacokinetics:
Plasma concentrations of GS-9876, filgotinib and an active filgotinib 
metabolite, GS-829845, will be analyzed. Urine concentrations of 
GS-9876, filgotinib, and GS-829845 may be analyzed.
Statistical Methods:
Analysis Methods:
The primary endpoint, the percent change from Baseline (Day 1) in 
24-hour proteinuria at Week 16, will be calculated for each treatment 
group and the 95% confidence interval will be constructed. 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. 
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). 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. 
Efficacy and safety data collected up to Week 16 will be summarized 
by treatment group for all subjects. Data from subjects who do not 
switch treatment will be summarized for the duration of the study by 
treatment group. Summaries by the combinations of treatment groups 
may be provided, if applicable.
The sample size was chosen based on the practical considerations and 
to ensure that a clinically meaningful reduction in proteinuria from 
Baseline (Day 1) could be detected in any of the treatment groups 
(filgotinib or GS-9876). With 16 subjects per treatment group 
(32 subjects total), there is a 80% power to detect a 35% reduction 
from Baseline (Day 1) in proteinuria at Week 16 with a standard 
deviation of 50% and a 2-sided 0.05 significance level.
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
ACEi
angiotensin-converting enzyme inhibitor 
ACR20
American College of Rheumatology 20% improvement
AE
adverse event
AhR
aryl hydrocarbon receptor
ALT
alanine aminotransferase
ANA
antinuclear antibody
Anti-dsDNA
anti-double stranded DNA
ARB
angiotensin II receptor blocker
AST
aspartate aminotransferase
ATP
adenosine triphosphate
AUC
area under the curve
BCR
b-cell receptor
BCRP
breast cancer resistance protein
bDMARDs
biologic disease-modifying antirheumatic drugs
BILAG
British Isles Lupus Activity Group Index
BLQ
Below the limit of quantitation
BMI
body mass index
Cave
average concentration
CD
cluster of differentiation
Cis
Confidence intervals
CIA
collagen-induced arthritis
CLE
cutaneous lupus erythematosus
Cmax
maximum observed plasma concentration
CNS
central nervous system
CRO 
Contract Research Organization
CYP
Cytochrome
DKD
Diabetic kidney disease
DMARDs
disease-modifying antirheumatic drugs
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DSS
Dextran sulphate sodium
EC50
geometric mean half-maximal effective concentration 
ECG
Electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
ESRD
end-stage renal disease
ET
early termination
EU
European Union


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FACS
Fluorescence-activated cell sorting
FAS
Full Analysis Set
FceRl
Fc epsilon Receptor I alpha
FDA
Food and Drug Administration
FFPE
formalin-fixed, paraffin-embedded
FSH
follicle stimulating hormone
FU
Follow-Up
GCP
Good Clinical Practice
GGT
gamma glutamyl transferase
GI
Gastrointestinal
GLPG
Galapagos
HBV
Hepatitis B virus
HCV
hepatitis C virus
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 Harmonization
IEC
Independent Ethics Committee
IFN
interferon
Ig
immunoglobulin
IL
interleukin
IMP
investigational medicinal product
INR
international normalized ratio
IP
interferon gamma-induced protein
IRB
Independent Review Board
IWRS
interactive web response system
JAK
janus kinase
LLOQ
lower limit of quantitation
LMN
lupus membranous nephropathy
MCV
mean corpuscular volume
MDRD
The Modification of Diet in Renal Disease Study
MTX
Methotrexate
NDA
New Drug Application
NOAEL
no-observed-adverse-effect level
NOELs
no observed effect levels
NSAID
nonsteroidal anti-inflammatory drugs


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NZB/NZW
New Zealand Black / New Zealand White (mouse strain)
OAT
organic ion transporter
PBMC
Peripheral blood mononuclear cells
PD
Pharmacodynamics
PE
Physical exam
P-gp
P-glycoprotein
PK
Pharmacokinetics
PT
preferred term
PTM
Placebo to match
PVE
Pharmacovigilance and Epidemiology (formally Drug Safety and Public Health –DSPH)
PXR
Pregnane x receptor
QTcF
QT interval corrected for heart rate according to Fridericia
RA
rheumatoid arthritis
RNA
ribonucleic acid
RR
respiratory rate
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
standard deviation
SELENA-SLEDAI
Safety of Estrogens in Lupus Erythematosus National Assessment Trial-Based SLE 
Disease Activity Index
SLE
Systemic lupus erythematosus
SOC
system organ class
STAT
signal transduction and activation of transcription
sTNFR2
soluble tumor necrosis factor receptor-2
SYK
spleen tyrosine kinase
TB
Tuberculosis
TEAEs
Treatment emergent adverse events
tmax
the time of occurrence of maximum observed plasma concentration
TNF
tumor necrosis factor alpha
TYK
tyrosine kinase
ULN
upper limit of normal
UPCR
urine protein to creatinine ratio 
US
United States
vfPBMCs
Viably frozen peripheral blood mononuclear cells
VL
Viral load
WBC
white blood cell


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1.
INTRODUCTION
1.1.
Background
Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory disease that affects 
approximately 1.5 million adults in the United States (US) {Sarpel 2016}. SLE manifests 
principally as an autoimmune disease characterized by autoantibodies to nuclear and cytoplasmic 
antigens that leads to protean manifestations that follows a relapsing and remitting course with 
considerable mortality, morbidity, and impact on quality of life. Although SLE has a variety of 
signs and symptoms, it often affects the joints, skin, brain, lungs, kidneys, and blood vessels. 
Patients with SLE may experience fatigue, pain or swelling in joints, skin rashes, and fevers. 
Although people of any age can be affected, the onset of SLE is most frequent between the ages 
of 15 and 44 years, and women are affected 4-12 times more often than men {Dall'Era 2013}. 
While the cause of SLE is still not completely understood, genetic, environmental, and hormonal 
factors may lead to autoreactive B-cells and T-cells, activation of the adaptive immune system, 
and perpetuation of inflammatory responses that have all been implicated in its pathogenesis.
Kidney involvement in SLE continues to be a major contributor to morbidity and mortality 
{Danila 2009}. Up to 50% of SLE patients will have clinically evident kidney disease at 
presentation, and during follow-up, kidney involvement may occur in over 60% of patients, with 
an even greater representation among children and young adults {Waldman 2006}. The type of 
renal disease can vary quite widely from asymptomatic hematuria and/or proteinuria to nephrotic 
syndrome and rapidly progressive glomerulonephritis.  One subtype of kidney disease is 
membranous nephropathy, which is a common cause of nephrotic syndrome in non-diabetic 
adults.  When it occurs in SLE patients it is considered to be a secondary cause of membranous 
nephropathy (class V lupus membranous nephropathy [LMN]) and occurs in 10-20% of patients 
with lupus nephritis {Danila 2009}.  Patients with LMN are at risk for developing end-stage 
renal disease (ESRD) due to protracted nephrotic syndrome.  In addition they are predisposed to 
hypercholesterolemia and hypertension, which contribute to accelerated atherosclerosis, as well 
as hypercoagulability and an increased risk of infection {Kolasinski 2002}.
There are limited studies investigating the benefit of disease-modifying antirheumatic drugs 
(DMARDs) or biologic disease-modifying antirheumatic drugs (bDMARDs) in the treatment of 
LMN {Austin 2009, Ginzler 2005, Hallegua 2000, Karim 2005, Kasitanon 2008, Mok 2004, 
Mok 2009, Yap 2012}.  In particular, randomized, controlled trials are lacking.  Prior studies 
support the use of prednisone and azathioprine {Mok 2004} mycophenolate mofetil {Ginzler 
2005, Karim 2005, Kasitanon 2008}cyclophosphamide {Austin 2009} sequential use of 
prednisone, cyclophosphamide, and azathioprine {Chan 1999} cyclosporine {Austin 2009, 
Hallegua 2000}, chlorambucil {Moroni 1998}, and plasmapheresis {Sloan 1996}.  However, 
these studies have been small, have used variable outcome measures, and have not always 
reported dose and duration of therapy.  There are no trials directly comparing 
immunosuppression versus non-immunosuppressive medications, and thus a consensus regarding 
optimal treatment does not exist.  Standard of care for LMN is controversial, but generally 
includes immunosuppression when high-grade proteinuria exists (> 3.5 g/day despite 


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non-immunosuppressive therapy) or serum creatinine progressively rises. Given the toxicity and 
variable efficacy of current immunosuppressive medications used in the treatment of LMN, there 
is an unmet need for a safer, more effective therapy.
Recent human studies reveal critical roles of Janus kinase (JAK) inhibition in the treatment of 
rheumatoid arthritis {Fleischmann 2012, Genovese 2016, Keystone 2015, Lee 2014, van 
Vollenhoven 2012}and psoriasis {Bachelez 2015}.  
Filgotinib (GS-6034, formerly GLPG0634) is a potent and selective oral inhibitor of JAK1 being 
developed by Gilead Sciences, Inc. (Gilead) and Galapagos (GLPG) NV. Filgotinib is effective 
in treating collagen-induced arthritis in rodents {Van Rompaey 2013}, and has demonstrated 
efficacy in two large Phase 2b clinical studies in subjects with RA. Upon activation, 
receptor-associated JAKs phosphorylate the intracellular portion of their receptors and provide a 
docking site for transcription factors known as signal transducers and activators of transcription 
(STATs) {O'Shea 2015}.  Activated STATs dimerize, enter the nucleus, bind DNA, and directly 
regulate gene expression.  A number of cytokines, growth factors, and hormones selectively act 
as ligands for one of four JAKs, leading to the preferential activation of 1 of 7 STATs.  Notably, 
JAK1 is responsible for signaling by inflammatory cytokines that are involved in autoimmune 
diseases, such as IFN- α, IFN-β, IFN-γ, IL-2, IL-6, IL-10, IL-15, and IL-21, amongst others 
{O'Shea 2015}.  
A study for the treatment of diabetic kidney disease (DKD) with baricitinib, a JAK1-2 selective 
inhibitor, indicated a dose-related reduction in albuminuria and inflammatory biomarkers 
involved in DKD progression, such as urinary interferon gamma-induced protein-10 (IP-10) and 
plasma soluble tumor necrosis factor receptor-2 (sTNFR2) {Brosius 2015, Tuttle 2015}.  
Although the exact pathogenesis of lupus, and more specifically lupus membranous nephropathy, 
are incompletely understood, it is believed that IFN-α {Feng 2006}, IL-10 {Houssiau 1995, 
Rahman 2008}, IL-21 {Bubier 2009, Sawalha 2008, Wang 2014}, and IL-6 {Maier-Moore 2014, 
Mao 2014, Sato 2014} play a role in SLE given their elevation and association with disease 
activity in lupus patients.  Signaling of these cytokines function through JAK 1 in SLE, and thus 
inhibition of this pathway with filgotinib may offer a rational therapeutic target.  
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 {Woroniecka 2011}. 
Signaling of these immune complex through SYK in various kidney diseases, and accumulating 
evidence from pre-clinical and clinical studies suggest a pathogenic role of SYK in proliferative 
glomerulonephritis, including anti-glomerular basement membrane disease, anti-neutrophil 
cytoplasmic antibody-associated glomerulonephritis, immunoglobulin A nephropathy, and lupus 
nephritis {Crispin 2010, Ma 2016}. 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 {Ryan 2016, Smith 2010}. Thus, inhibition of 
the SYK pathway with GS-9876 may offer a rational therapeutic target in lupus nephritis.  


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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.
Preclinical 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 Central Nervous 
System (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 were the lymphoid tissues which are expected based on the pharmacology of JAK 
inhibition. Additional filgotinib-related findings were observed in the male reproductive organs 
of both species, and in the incisor teeth of rats. Effects on the lymphoid system were fully 
reversible. Testicular toxicity demonstrated partial reversibility, however sperm counts remained 
low. A dose of 200 mg once daily of filgotinib results in an estimated mean clinical area under 
the curve (AUC) of 2.80 μg∙h/mL in rheumatoid arthritis (RA) subjects, which represents an 
exposure margin of 2.3, 1.8, and 3.4-fold when considering the mean AUC in male dogs at the 
no-observed-effect-levels (NOELs) in the 26-week and 39-week chronic toxicity studies and the 
39-week targeted exposure toxicity study, respectively. GS-829845-related findings in general 
repeat dose toxicity studies were similar to those of the parent filgotinib, however no testicular 
toxicity was noted following administration of GS-829845.
Filgotinib and GS-829845 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.


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1.2.3.
Clinical Trials of Filgotinib
As of April 2017, filgotinib has been taken by more than 1400 subjects, including more than 
950 with RA and more than 150 subjects with Crohn’s disease, and has been generally safe and 
well tolerated. Clinical trials of filgotinib have not been previously undertaken in subjects with 
LMN. A detailed description of all clinical studies can be found in the IB.
In 9 Phase 1 studies conducted in healthy subjects (Studies GPLG0634-CL-101, -102, -103, 
-104, -105, -106, -107, -110, and GS-US-417-3900), filgotinib administered at doses of up to 
450 mg once daily for up to 10 days was safe and well tolerated.
In 2 Phase 2a studies in subjects with RA (Study GLPG0634-CL-201 and -202), dosing with 
filgotinib was well tolerated and achieved maximal efficacy at a 200 mg daily dose 
(American College of Rheumatology 20% improvement [ACR20] response of 75-92% at 
Week 4).
In 2 Phase 2b studies, filgotinib at total daily doses of 50 mg, 100 mg, or 200 mg, administered 
in addition to background therapy with methotrexate (MTX) (GLPG0634-CL-203) or as 
monotherapy (GLPG0634-CL-204) was safe and effective in subjects with moderately to 
severely active RA who had an inadequate response to MTX alone.
Safety data collected across Phase 2 clinical studies in RA and Crohn’s Disease showed no 
dose-dependent trends in the incidence of adverse events (AEs) or serious adverse events 
(SAEs), including infections, or laboratory abnormalities with the exception of a numerical 
increase in select gastrointestinal AEs (eg, nausea, vomiting, abdominal pain, and upper 
abdominal pain). This numerical increase was observed in the 200 mg compared to the 100 mg 
dose. However, the overall frequency was low and clinical relevance is unknown. The safety 
profile of filgotinib was consistent with that observed for an immunomodulatory compound 
administered to subjects with RA.
1.3.
GS-9876 
For further information on GS-9876, refer to the current IB.
1.3.1.
Nonclinical Pharmacology and Toxicology
1.3.1.1.
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 
of differentiation (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 


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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 with GS-492429, a compound with similar 
selectively as GS-9876, showed a dose-responsive decrease in anti-dsDNA antibody titers and 
inhibition of proteinuria 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. This confirmed previously published 
data from the study of the SYK inhibitor, fostamitinib, in a NZB/NZW murine model and in a
MRL/lpr murine model that demonstrated delayed onset of proteinuria and azotemia, reduced 
renal pathology and kidney infiltrates in lupus-prone mice {Bahjat 2008, Deng 2010}
In 2 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. 
1.3.1.2.
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 


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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 at the high dose of 15 mg/kg/day, 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-437-4093, 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-437-4093, 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. 
Table 1-1.
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


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1.3.1.3.
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 (OATP1B1 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.
1.3.2.
Clinical Trials of GS-9876
As of February 2016, 62 healthy volunteers have been dosed with GS-9876 in two clinical 
studies.
1.3.2.1.
Completed Clinical Trial
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 
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. 
1.3.2.2.
Ongoing Clinical Trials
GS-US-379-1582: This is a 12 week proof of concept trial of GS-9876 in patients with RA to 
evaluate efficacy, safety, tolerability, and PK of GS-9876.
GS-US-379-1932: This is a Phase 1, open-label, parallel-group, adaptive, single-dose, 
multi-center, PK study in subjects with renal impairment and matched healthy controls.
Preliminary PK results showed no change in GS-9876 PK by moderate renal impairment. 


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GS-US-445-4189: This is a 48 week proof of concept trial of GS-9876 in patients with Sjogren’s 
syndrome to evaluate efficacy, safety, tolerability, and PK of GS-9876.
1.4.
Rationale for This Study
Although patients with LMN are at increased risk for end-stage renal disease, thromboembolic 
events and transition to proliferative lupus nephritis, therapeutic options for LMN are limited 
{Swan 2011}. There are very limited clinical trial data in LMN for the various newer biologic 
and synthetic DMARDs that have been approved for other indications. Prior studies support the 
use of prednisone and azathioprine {Mok 2004, Mok 2009}, mycophenolate mofetil {Ginzler 
2005, Karim 2005, Kasitanon 2008}, cyclophosphamide {Austin 2009} sequential use of 
prednisone, cyclophosphamide, and azathioprine {Chan 1999}, cyclosporine {Austin 2009, 
Hallegua 2000}, chlorambucil {Moroni 1998}, and plasmapheresis {Sloan 1996}.  However, 
these investigations have been small, have used variable outcome measures, and have not always 
reported dose and duration of therapy. In addition, some individuals with LMN have an 
inadequate response or intolerance to available therapies. Thus, 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. JAK1 activation is required for type I interferon (IFN) 
signaling, which is thought to be central to both systemic lupus and lupus nephritis. Although in 
vivo studies using a JAK inhibitor attenuated the progression of renal inflammation in the 
MRL/lpr mouse model of lupus using AG490 (JAK 2 inhibitor) {Wang 2010}, as well as the 
NZB/WF1 mouse model of lupus using CP-690,550 (JAK3 inhibitor) {Ripoll 2016}, there are no 
published data regarding JAK1 inhibition. However, preclinical studies at Gilead in MRL/lpr 
mice suggest mild reduction in proteinuria with JAK1/3 inhibition, and even greater 
effectiveness when combined with a SYK inhibitor.  
Given its central role in immune cell signaling, inhibition of SYK is expected to have pleiotropic 
anti-inflammatory effects and affect multiple steps in lupus nephritis pathogenesis. Compared 
with normal T cells, T cells obtained from lupus patients demonstrated substantially higher SYK
expression and activity {Krishnan 2008}In addition, B cells have been implicated in the 
pathogenesis of lupus nephritis, and B cell depletion demonstrates an effect in individuals with 
certain types of LMN {Ulinski 2014}. As a critical mediator of BCR signaling, SYK inhibition 
suppresses BCR-stimulated proliferation, co-stimulatory molecule expression, and autoantibody 
production {Braselmann 2006, Coffey 2012}. Further, inhibiting SYK in vitro delays the onset 
of proteinuria and azotemia, reduced renal pathology and kidney infiltrates and significantly 
prolonged survival in lupus prone NZB/NZW mice {Bahjat 2008}. In MRL/lpr mice, inhibiting 
SYK prevented the development of renal disease and reduced proteinuria in established disease 
{Deng 2010}
The data suggest that inhibition of SYK or of JAK1 may decrease several processes implicated 
in LMN pathophysiology including B-cell and T-cell activation.


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1.4.1.
Rationale for Endpoint and Timing
Change in proteinuria will be the primary measure of efficacy. Proteinuria has long been used as 
a surrogate endpoint because it correlates well with kidney function, and it has been implicated 
in the pathogenesis of chronic kidney disease. In LMN it is associated with thromboembolic 
events, as well as cardiovascular events. Proteinuria is a standardized outcome measure of lupus 
nephritis, and an attractive choice because following an intervention, the change in proteinuria is 
often earlier and larger than the observed change in kidney function. It might be useful therefore 
in slowly progressive or early stages of disease. A magnitude of 35% or greater reduction in 
proteinuria was selected based on response rates observed during other trials of lupus nephritis 
{Borchers 2012}, including LMN {Swan 2011}.
Secondary measures will include additional measures of kidney structure and function 
(eg, proteinuria and glomerular filtration rate) at various time points, as well as measures of 
lupus activity. Validated scales will be used for lupus, including the Safety of Estrogens in Lupus 
Erythematosus National Assessment trial-based SLE Disease Activity Index 
(SELENA-SLEDAI) and the British Isles Lupus Activity Group (BILAG). 
The selection of the 16-week time point is based on prior studies of LMN and lupus nephritis 
more broadly, as well as 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 lupus nephritis {Borchers 2012} including LMN {Swan 2011}, 
demonstrates a range of drug administration duration between 10 weeks for cyclophosphamide 
and 6 months for azathioprine and mycophenolic acid, supporting the idea that a 16-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) or GS-9876 
(30 mg) with matched placebo tablets. The planned treatment of filgotinib and GS-9876 is based 
on safety data from clinical studies and supported by non-clinical safety data. Clinical efficacy 
data in RA further support the filgotinib dose.
Results from Phase 2a studies (GLPG0634-CL-201 and GLPG0634-CL-202) and Phase 2b 
studies (GLPG0634-CL-203 and GLPG0634-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 of AEs or SAEs. Based on the overall risk-benefit 


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observed in Phase 2b studies, as well as some clinical similarities of RA and systemic lupus 
erythematosus, 200 mg once daily filgotinib is expected to be a safe dose to evaluate efficacy in 
subjects with LMN.
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 systemic lupus erythematosus, a 30 mg once daily dose is expected to have an 
acceptable safety profile and have the potential to be efficacious in LMN.
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. It is proposed to study filgotinib in LMN at a dose of 200 mg once daily, a 
dose at which maximal clinical benefit has been observed for subjects with active RA.
Filgotinib has been administered in large Phase 2b studies of subjects with RA and Crohn’s 
Disease 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 was observed in Phase 1 and 2 trials of filgotinib.
In the Phase 2b studies in RA, the most common AEs were in the infections and infestations 
system organ class (SOC), and infections were reported more commonly in the filgotinib groups. 
Pneumonia is an identified risk and serious infection is considered an important potential risk for 
filgotinib. Reference is made to the IB for further information about clinical infection findings.
As filgotinib is an immunomodulating agent, malignancy is closely monitored in clinical studies 
with filgotinib. 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 
for filgotinib. Reference is made to the IB for further information about clinical malignancy 
findings, carcinoma, and nonmelanoma skin cancers. All reported malignancies occurred in 
subjects with RA. 
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 


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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. The clinical relevance of nonclinical testicular findings in rats and dogs is 
unknown. A male safety study is planned to assess the effects, if any, of filgotinib on semen 
parameters in males with inflammatory diseases. Until the definitive results of this study are 
available, all males will be informed about this potential toxicity in the informed consent form 
and only men understanding and accepting the potential risk for loss of fertility will be enrolled. 
In addition, SLE is a disease of female predominance and although this may vary across some
study populations, the ratio of those affected is approximately 9 fold higher in females than 
males. Reference is made to the IB for further information about nonclinical and clinical 
testicular findings.
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. Based on available non-clinical findings, GS-9876 is not 
contraindicated in pregnancy, although pregnancy in GS-9876 trials should be avoided. 
Measures to minimize other potential risks to subjects will include site/investigator training 
regarding monitoring for infection. 
Preclinical and clinical data support the further clinical development of GS-9876 and filgotinib 
due to their potential benefit as novel therapies in lupus nephritis, 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 
lupus nephritis and related diseases.
1.6.
Compliance
This study will be conducted in compliance with this protocol, GCP, and all applicable 
regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of filgotinib and GS-9876 in subjects with LMN
The secondary objectives of this study are: 

To evaluate the safety and tolerability of filgotinib and GS-9876 in subjects with LMN

To evaluate the PK of filgotinib and GS-9876 in subjects with LMN
The exploratory objectives of this study are:
 
 
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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint of this study is:

The percent change in urine protein from Baseline (Day 1) to Week 16 (assessed by urine 
protein excretion during a 24-hour urine collection)
The secondary endpoints of this study are:

Change from Baseline (Day 1) in urine protein (assessed by urine protein excretion during a 
24-hour urine collection) at Week 16

Change from Baseline (Day 1) in eGFR at Week 16

Change from Baseline (Day 1) in UPCR (assessed by urine protein excretion during a 
24-hour urine collection) at Week 16

Proportion of subjects with partial remission (defined as urine protein excretion below 
< 3 g/d and urine protein excretion decrease by ≥ 50% among subjects with Baseline (Day 1) 
nephrotic range proteinuria [urine protein excretion ≥ 3 g/d]; or urine protein excretion 
decrease by ≥ 50% among subjects with subnephrotic range proteinuria [urine protein 
excretion < 3 g/d]) at Week 16

Proportion of subjects with complete remission (defined as urine protein excretion below 
0.5 g/day, with no hematuria) at Week 16
The exploratory endpoints of this study are:
 
 
 
 
 
 
 
 
 
 
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The biomarker endpoints of this study are:

Change in JAK-STAT-, SYK-, and disease-related biomarkers in peripheral blood and urine

Association of changes in peripheral blood and urine biomarkers with clinical outcomes

Association of Baseline markers with disease severity and response to filgotinib and 
GS-9876
3.2.
Study Design
This is a Phase 2, randomized, double-blind, multicenter study to evaluate the safety and efficacy 
of filgotinib and GS-9876 in subjects with active LMN who are not in partial or complete 
remission in response to treatment with one or more anti-inflammatory or immunosuppressive 
agents.
A schematic of this study is provided in Figure 3-1.
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Figure 3-1.
Study Schema
3.3.
Study Treatments
Eligible subjects will be randomized in a 1:1 ratio to receive once daily oral doses of the 
following study drugs for 16 weeks:
Arm
Study Drugs
Filgotinib (n=16)
Filgotinib 200 mg + PTM GS-9876
GS-9876 (n=16)
GS-9876 30 mg + PTM Filgotinib
PTM = Placebo to match
Randomization will be stratified by prior treatment with cyclophosphamide. 
Urinary protein excretion will be determined using 2 methods – two consecutive morning voids 
as well as a 24-hour urine collection. For the Day 1 assessment, all 3 urine samples will be 
collected prior to Day 1, with the 24-hour urine collection as close to the Day 1 visit as possible. 
At Week 16, the primary study endpoint will be assessed by urine protein excretion during a 
RANDOMIZATION 
1:1 
(N=32) 
DAY1 
Basefine 
Blinded Treatment Phase 
WK16 
1• Endpoint 
Gs-9876 30 mg+ 
PTM Filgotinib 
I 
' 
I 
" 
WK 16: S.ul>jectswith a 23556 reduction in 
urinary protein excretion from Baseline (Day l j 
to \Ve.e. 16will continue to rec.eiv.e their 
as,s ign ed l>li nd ed study tre3tment for an 
additional 16wceks. 
Sul>jects th 3tdo notach ieve a 2 3 556 reduction 
in urinary prote in -e.m:.ratioo w i II S1.vitch study 
treatment 
Extended Blinded 
Treatment Phase 
WK32 
'f 
Filgotinib200 mg+ 
PTM GS-9876 
GS-9876 30 mg + 
PTM Filgotinib 
GS-9876 30 mg+ 
PTM Filgotinib 
Filgotinib200 mg+ 
PTM GS-9876 
WK 32: Sul>jectswith a 2 3556 reduction in urinary 
protein ,e>e:retion from Dayl [forsul>jectswho 
remained on the r.andommed studytr:eatm.entaft2r 
W eek 16) or from W eek 16 {for su l>jects who 
switc.hed trc3tmentatWeek l6j w illcontinueto 
receiv.eth eirassigned blinded studytreatmentfor 
an additi::in3120wee·ks. 
S.ub-jectst.hatdo notachieve al 35% reduction in 
urin ary J>roteinexcretion from Day 1 {for subjects 
who r2m 3ined on the ranclomiz-ecl studytr.e3tment 
aft.2r't;'•'.eek 16)orfrom 'llleek 16{fors.Libject.swho 
5witc.hed tre3tment atW eek 16j toWeek 32 can 
cont:in uewh ichever tre.atment led to the gre3test 
reduction in urinary p-rotein.excrettcln [from Dav 1 
to 'W e,ek 1£.on initial studytr:Eatmentorfrom 
We€k 16toWeek32 on switched treatment!, or 
eit:h.er study tr eatment p.erth.e lnve::i""tigamr's 
discretion. 
WK52 WK56 
Follow-Up 


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24-hour urine collection. Two consecutive morning voids prior to the Week 16 visit will be used 
to determine response for subsequent study treatment. All subjects who achieve a 
≥35% reduction in urinary protein excretion (using an average of the UPCR from 2 morning 
voids) from Day 1 will continue to receive their assigned blinded study treatment
(filgotinib 200 mg + PTM GS-9876, or GS-9876 30 mg + PTM filgotinib) for an additional 
16 weeks. Additional details regarding urine collection procedures will be specified in the 
Laboratory Manual and Subject Procedures Manual.
Subjects who do not achieve a ≥ 35% reduction in urinary protein excretion from Day 1 to 
Week 16 will switch study treatment for 16 weeks in a blinded fashion (ie, those on filgotinib 
will switch to GS-9876 + PTM filgotinib, while those on GS-9876 will switch to 
filgotinib + PTM GS-9876). 
After 32 weeks of blinded treatment, those who have a ≥ 35% reduction in urinary protein 
excretion (using an average of the UPCR from 2 morning voids) from Day 1 (for subjects who
remained on the randomized study treatment after Week 16) or from Week 16 (for subjects who 
switched treatment at Week 16) will continue their assigned blinded treatment for an additional 
20 weeks in the Extended Blinded Treatment Phase.  Subjects that do not achieve a 
≥35% reduction in urinary protein excretion from Day 1 (for subjects who remained on the 
randomized study treatment after Week 16) or from Week 16 (for subjects who switched 
treatment at Week 16) to Week 32 will be allowed to continue whichever treatment led to the 
greatest reduction in urinary protein excretion (from Day 1 to Week 16 on initial study treatment 
or from Week 16 to Week 32 on switched treatment), or either study treatment per the 
Investigator’s discretion (eg, differences in tolerability or other non-renal benefits that support 
overriding the treatment assignment according to reduction in urinary protein excretion) during 
the Extended Blinded Treatment Phase.
3.4.
Duration of Treatment
Eligible subjects will receive a maximum of 52 weeks of study drug.
3.5.
Discontinuation Criteria
3.5.1.
Study Drug Interruption Considerations
The Gilead Sciences, Inc. (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 
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
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.
3.5.2.
Study Drug Discontinuation Criteria
The Gilead Medical Monitor should be consulted prior to study drug discontinuation when 
medically 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 Serious Adverse Event (SAE) reporting criteria

Complicated herpes zoster infection (with multi-dermatomal, disseminated, ophthalmic, 
or CNS involvement)

Evidence of active HCV during the study, as evidenced by HCV ribonucleic acid (RNA) 
positivity

Evidence of active HBV during the study, as evidenced by HBV deoxyribonucleic acid 
(DNA) positivity or HBV core antibody 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

Pregnancy during the study; refer to Section 7.7.2.1

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board (IRB)


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
Subject use of prohibited concurrent therapy may trigger study drug discontinuation; 
consultation should be made with the Gilead Medical Monitor.

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 for lack 
of efficacy but may continue with study visits per investigator judgment; refer to 
Section 5.3.1.1

Laboratory Criteria: After becoming aware of any of the following abnormal laboratory 
values, 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 discontinued and further care of the 
subject should be directed per the investigator.
a) Neutrophils < 1.0 103 cells/mm3 (SI: < 1.0 109 cells/L)
b) Hemoglobin < 8.0 g/dL (SI: < 80 g/L)
c) Platelets < 75.0 103 cells/mm3 (SI: < 75.0 109 cells/L)
d) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the 
upper limit of normal range (ULN) AND total bilirubin > 2 ULN or accompanied by 
symptoms consistent with hepatic injury1
e) AST and/or ALT elevations > 3 ULN accompanied by elevated international 
normalized ratio (INR) 1
f)
AST or ALT > 5 ULN1
g) Estimated glomerular filtration rate (eGFRMDRD) < 40 mL/min/1.73 m2 based on the 
MDRD 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 20-week Extended Blinded Treatment Phase. Subjects who permanently 
discontinue study medication for any reason will not be replaced.  Subjects withdrawing from the 
study should complete the early termination (ET) and Final 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). 
                                                
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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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 52 weeks of dosing plus the 
follow-up visit 4 weeks (± 5 days) after the last dose of study drug (ie, Week 56).
3.7.
Post Study Care
The long-term care of subjects post-study will remain the responsibility of their primary treating 
physician.
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 events and to help inform the mechanism of action
and mechanisms of resistance to filgotinib and GS-9876 in lupus nephritis. The specific analyses 
may include, but will not be limited to, the assays listed below.  
The biomarker analyses may include the following:

Measuring the expression and phosphorylation state of STAT and SYK proteins

Characterization of tissue lymphocyte subsets

Plasma and serum samples for analysis of circulating factors including but not limited to 
cytokines, microRNA, and metabolites.

Urine samples for analysis of excreted biomarkers associated with nephritis.

PBMC samples to assess cell phenotype.

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. 


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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 Laboratory Manual.
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
CCI
CCI
CCI
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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 32 subjects with LMN.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) Able and willing to sign the informed consent as approved by the Institutional Review Board 
(IRB). Written consent must be provided before initiating any screening evaluations. 
Subjects must have read and understood the informed consent form (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 understand the ICF may not be enrolled by a 
guardian or any other individual
2) Male or female between 18 and 75 years of age, inclusive, at the time of initial informed 
consent
3) Kidney biopsy within the 36 months prior to Screening with a histologic diagnosis of LMN 
(International Society of Nephrology [ISN] and the Renal Pathology Society [RPS] 2003 
classification of lupus nephritis), either Class V alone, or Class V in combination with
Class II. If the biopsy indicates segmental glomerular scarring indicative of prior Class III or 
IV lesions but there is limited or no evidence of current Class III or IV activity, the subject 
would be eligible if the Class V findings are active. 
A copy of the kidney biopsy pathology report will be obtained from each subject and 
forwarded to the Gilead Medical Monitor for review and confirmation of eligibility prior to 
randomization on Day 1.
4) Urine protein excretion ≥ 1.5 grams per day based on 24-hour urine sample collected during 
Screening
5) Estimated glomerular filtration rate (eGFRMDRD) ≥ 40 mL/min/1.73 m2 based on the MDRD 
formulation at Screening 
6) Prior treatment for LMN with at least one immunosuppressive therapy for a sufficient 
duration before Screening, including but not limited to:
a) Calcineurin inhibitors (cyclosporin A, tacrolimus), 
b) Alkylating agents (chlorambucil, cyclophosphamide), or
c) Antimetabolite drugs (azathioprine, mycophenolate mofetil) 
d) Other (eg, methotrexate, leflunomide, moderate- to high-dose steroids, etc.)
A brief Investigator summary of prior therapy should be provided (ie, therapy name, 
duration/dates, and response).


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7) Treatment with an ACEi or ARB at a dose deemed appropriate for the subject per the 
Investigator for at least 6 weeks prior to and during Screening, with a stably prescribed dose
for at least 14 days prior to Day 1. Enrolled subjects should remain on the stably prescribed 
dose of ACEi or ARB treatment throughout the study.
Subjects who are not taking any ACEi or ARB may be screened if there is documented 
intolerance to ACEi and/or ARB  
8) If a subject is taking oral glucocorticoids, the dose must be ≤ 20 mg/day prednisone 
(or equivalent) and must have been on a stably prescribed dose for at least 28 days prior to 
Day 1. Enrolled subjects should remain on the stably prescribed dose of prednisone treatment 
through Week 16 of the study (after assessment of the primary outcome). 
9) If a subject is taking the following agents, they must have been on a stably prescribed dose
for at least 28 days prior to Day 1:
a) Hydroxychloroquine (≤400 mg/day),
b) Chloroquine (≤ 250 mg/day), or
c) Quinacrine (≤ 100 mg/day)
Enrolled subjects should remain on the stably prescribed dose of the above treatments
throughout the study.  
10) Use of NSAIDs is permitted if the dose has been stably prescribed for at least 14 days prior 
to Day 1. Enrolled subjects should remain on the stably prescribed dose of NSAID treatment 
throughout the study. Intermittent use (PRN) for non-LMN indications should be minimized.
11) All DMARDs or immunosuppressive agents other than glucocorticoids, hydroxychloroquine
(as specified above), azathioprine (up to a maximum of 2 mg/kg body weight/day or 
200 mg/day, whichever is lower), and methotrexate (≤ 20 mg per week) should be withdrawn 
at least 28 days prior to Day 1.
12) Systolic blood pressure (SBP) below 160 mmHg AND diastolic blood pressure (DBP) below 
90 mmHg will be measured at Screening. The Screening blood pressure may be repeated (a 
maximum of 2 times) as an unscheduled visit prior to Day 1.
13) Females of childbearing potential (as defined in Appendix 5) must have a negative pregnancy 
test at Screening, Day 1 and throughout the study at each study visit.
14) Male subjects and female subjects of childbearing potential who engage in heterosexual 
intercourse must agree to use protocol specified method(s) of contraception as described in 
Appendix 5. Specifically, female subjects must agree to refrain from attempting conception, 
egg donation or harvest from the time of signing consent through 36 days following the last 
dose of study drug. Male subjects must agree to refrain from attempting conception, or sperm 
donation from the time of signing consent through 90 days following the last dose of study 
drug.


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15) Subjects must agree to refrain from blood donation from Screening through at least 30 days 
following the last dose of study drug.
16) Lactating female subjects must agree to discontinue nursing from Screening through at least 
36 days following the last dose of study drug.
17) Meet the following TB Screening criteria: 
a) No evidence of active or latent TB as assessed during Screening by:

A negative QuantiFERON® TB-Gold In-Tube test at Screening AND

A chest radiograph (if consistent with local guidelines) taken at Screening or within 
the 90 days prior to Screening (with the report or films available for investigator 
review) without evidence of active or latent TB infection 
b) Subjects previously treated for latent TB: subject who has previously received an 
adequate course of therapy as per local standard of care for latent TB (eg, 9 months of 
isoniazid in a location where rates of primary multi-drug resistant TB infections are 
<5% or an acceptable alternative regimen). In these cases, no QuantiFERON® TB-Gold 
In-Tube test (or equivalent assay) need be obtained, but a chest radiograph must be 
obtained if not done so within 90 days prior to Screening (with the report or films 
available for Investigator review). It is the responsibility of the Investigator to verify the 
adequacy of previous anti-tuberculosis treatment and provide appropriate documentation.  
Subjects with a history of untreated or inadequately treated latent TB are excluded from 
the study.
c) Subjects with newly identified latent TB during Screening are excluded from the study.  
Cases falling under category “b” need to be approved by the Sponsor prior to  enrollment in 
the study. Subjects with any history of or current active TB (regardless of past or present 
anti-TB treatment) are excluded. 
18) In the judgment of the investigator, participation in the study offers an acceptable benefit/risk 
ratio when considering current lupus membranous nephropathy disease status, medical 
condition, and the potential benefits and risks of alternative treatments for lupus membranous 
nephropathy
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Prior treatments as follows:
a) Previous treatment with a JAK inhibitor within 3 months of Day 1


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b) Use of rituximab or other selective B lymphocyte depleting agents 
(including experimental agents) within 6 months of Day 1. Enrollment is permitted if the 
last dose was given > 6 months and CD19-positive B cells are detectable at Screening.
c) Anticipated use of disallowed medications in Section 5.3.2
2) Known hypersensitivity or allergy to the study drugs (filgotinib, GS-9876), their metabolites, 
or formulation excipients 
3) History of, or current, inflammatory or autoimmune disease other than SLE 
(e.g., scleroderma, reactive arthritis, rheumatoid arthritis, ankylosing spondylitis, 
Lyme disease) that will interfere with clinical evaluation during the study, per judgment of 
the Investigator. Secondary Sjogren’s Syndrome or controlled thyroiditis is acceptable, per 
judgment of Investigator
4) Administration of a live/attenuated vaccine within 30 days prior to Day 1, or planned during 
the study or through 12 weeks after subject’s last dose of study drug
5) Participation in any clinical study of an investigational drug/device within 4 weeks or 
5 half-lives prior to Screening, whichever is longer. Exposure to investigational biologics 
should be discussed with the Sponsor
6) End stage renal disease (ESRD; peritoneal dialysis, hemodialysis, or status post-renal 
transplantation) 
7) History of lymphoproliferative disease or current lymphoproliferative disease 
8) History of organ or bone marrow transplant
9) Positive serology for human immunodeficiency virus (HIV) 1 or 2 at Screening
10) Evidence of active HCV infection. Subjects with positive HCV Ab at Screening, 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. Subjects with active HCV during the study, as evidenced by RNA positivity, 
will be discontinued from study drug as outlined in the protocol.
11) Evidence of active or prior HBV infection. Subjects with positive HBV surface antigen 
(HBsAg) at Screening are excluded from the study. Subjects with positive HBV DNA or 
HBV core Ab are excluded from the study.
12) History of opportunistic infection, or immunodeficiency syndrome, which would put the 
subject at risk, as per investigator judgment.


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13) Active infection that is clinically significant, as per judgment of the investigator, or any 
infection requiring hospitalization or treatment with intravenous anti-infectives within 
60 days of Day 1; or any infection requiring oral anti‑infective therapy within 30 days of 
Day 1.  
14) Currently on any treatment or prophylaxis for chronic infection (such as pneumocystis, 
cytomegalovirus, herpes zoster, and atypical mycobacteria). Past history of disseminated 
Staphylococcus aureus or disseminated Herpes simplex infection. 
15) History of symptomatic herpes zoster infection within 12 weeks prior to Screening or history 
of disseminated/complicated herpes zoster infection (multi-dermatomal involvement, 
ophthalmic zoster, central nervous system involvement or postherpetic neuralgia)
16) 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 5.3.2  (NOTE: stably prescribed chronic aspirin therapy ≤325 mg/day for 
cardiovascular prophylaxis is allowed).
17) History of an infected joint prosthesis or other implanted device with retention of the 
prosthesis or device in situ
18) Current drug or alcohol abuse, per investigator judgment
19) History of or current moderate to severe congestive heart failure (New York Heart 
Association [NYHA] class III or IV), OR within the last 6 months, a cerebrovascular 
accident, myocardial infarction, unstable angina, unstable arrhythmia, OR new or significant 
ECG finding at Screening, or any other cardiovascular condition which, in the opinion of the 
investigator, would put the subject at risk by participation in the study.
20) History of malignancy within the past 5 years prior to Screening (except for adequately 
treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin or
cervical carcinoma in situ, with no evidence of recurrence). 
21) Significant blood loss (> 450 mL) or transfusion of any blood product within 12 weeks prior 
to Day 1.
22) Tests performed at the central laboratory at Screening that meet any of the criteria below 
(out of range lab values that are believed to be in error may be rechecked one time, after 
consultation with the sponsor or its designee, before subject is considered a screen failure):
a) Hemoglobin < 8.0 g/dL (International System of Units [SI]: < 80 g/L);
b) Neutrophils < 1.5 103 cells/mm3 (SI: < 1.5 109 cells/L);
c) Platelets < 100 103 cells/mm3 (SI: < 100 109 cells/L);


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d) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥1.5 ULN;
e) Total bilirubin level ≥2 ULN unless the subject has been diagnosed with Gilbert’s 
disease and this is clearly documented;
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 
tests/procedures 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 emergency medical care for the subject. The 
rationale for unblinding must be clearly explained in source documentation and on the case 
report form/ electronic case report form (eCRF), along with the date on which the treatment 
assignment was unblinded. 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.
Gilead Pharmacovigilance and Epidemiology (PVE) may independently unblind cases for 
expedited reporting of suspected unexpected serious adverse reactions (SUSARs).
5.2.
Description and Handling of GS-9876, PTM GS-9876, Filgotinib and PTM 
Filgotinib
5.2.1.
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. 
Matching placebo tablets will be supplied that are identical in physical appearance to the 30 mg 
GS-9876 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.


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5.2.2.
Formulation of Filgotinib and PTM Filgotinib
Filgotinib will be provided as 200 mg tablets that are capsule-shaped, and film-coated beige 
debossed with “GSI” on one side and “200” on the other. 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.
PTM filgotinib tablets are identical in appearance to the active filgotinib tablets. PTM filgotinib 
tablets contain the following inactive ingredients: microcrystalline cellulose, lactose 
monohydrate, croscarmellose sodium, magnesium stearate, macrogol/PEG 3350, polyvinyl 
alcohol, talc, titanium dioxide, iron oxide yellow, and iron oxide red.
5.2.3.
Packaging and Labeling of Study Drugs
GS-9876 tablets, 30 mg, filgotinib tablets, 200 mg, and PTM 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 with an induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA) and/or other local regulations.
5.2.4.
Storage and Handling of Study Drugs
GS-9876 tablets, filgotinib tablets, and PTM tablets should be stored at a 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 bottles of 
study drugs should be stored in a securely locked area, accessible only to authorized site 
personnel.
To ensure the stability and proper identification, study drugs should not be stored in a container 
other than the container in which they were supplied.  Keep the container tightly closed to 
protect from moisture.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure when handling.  


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Amendment 2
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5.2.5.
Dosage and Administration of GS-9876
GS-9876 30 mg (1 30 mg tablet), or GS-9876 PTM (1 tablet) will be provided by Gilead 
Sciences, Inc. and are to be administered orally once daily with water. The study drug should be 
swallowed whole. GS-9876 or GS-9876 PTM may be taken with or without food. Each subject 
will be given instructions to maintain approximately the same daily dosing interval between 
study drug doses. Subjects will be instructed to take study drug at approximately the same time 
each morning. At Weeks 2, 4 and 20, subjects will be instructed to take their study drug in clinic 
as the first study procedure prior to any others scheduled for that visit. At Weeks 16 and 
32 subjects will be instructed to take their study drug after predose assessments have been 
completed (eg, PK sample collection).
For missed dose(s) of study medication, subject should be instructed to take the missed dose(s) 
of study medication, as soon as possible, during the same day. If more than 8 hours has elapsed 
since the scheduled time of the missed dose, the subject should be instructed to wait and take the 
next dose at the regularly scheduled time. Subjects should be cautioned never to double the next 
dose with a missed dose of study drug under any circumstances. 
5.2.6.
Dosage and Administration of Filgotinib
Filgotinib 200 mg tablets and PTM filgotinib 200 mg tablets 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. 
At Weeks 2, 4 and 20, subjects will be instructed to take their study drug in clinic as the 
first study procedure prior to any others scheduled for that visit. At Weeks 16 and 32 subjects 
will be instructed to take their study drug after predose assessments have been completed (eg, PK 
sample collection).
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 more than 8 hours has elapsed 
since the scheduled time of the missed dose, the subject should be instructed to wait and take the 
next dose at the regularly scheduled time. 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.
5.3.
Prior and Concomitant Medications
All medications taken for the treatment of lupus and lupus nephritis will be recorded in the 
source documents and on the eCRF. All other medications (for non-SLE 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.


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Gilead Sciences, Inc. 
Amendment 2
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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, and instruct subjects to hold study drug 
administration while taking an excluded medication.
5.3.1.
Allowed Concomitant Medications 
5.3.1.1.
Concomitant Medications for LMN
The allowed concomitant medication(s) for LMN should be maintained, as much as possible, at 
stable doses (defined as no change in prescription) 28 days prior to Day 1 through Week 16:

Oral corticosteroids for SLE ≤ 20 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 SLE (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 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

Oral azathioprine (≤2 mg/kg bodyweight/day or 200 mg/day, whichever is lower) for SLE or 
lupus nephritis (administered per investigator judgment). Subjects who are not planning to 
continue oral azathioprine during the study must have discontinued them at least 28 days 
prior to Day 1  
After completion of the Week 16 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 for lack of 
efficacy but may continue with study visits per investigator judgment.


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Amendment 2
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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. 
5.3.1.2.
Other Concomitant Medications
The following concomitant medications should be maintained, as much as possible, at stable 
doses 28 days prior to Day 1 and throughout the duration of the study.

Vitamins, minerals, and herbal supplements

Hormonal contraceptives or male or female hormone replacement therapy

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
5.3.2.
Prohibited Concomitant Medications 
Examples of prohibited medications are provided below. This list does not include medications 
such as anti-HIV agents that would be contraindicated based on other exclusion criteria.
Table 5-1.
Prohibited Medications
Drug Class
Agents Disallowed
Prohibited Period
Biologic Immunomodulator
Anti-tumor necrosis factor drugs infliximab, 
adalimumab, belimumab, golimumab, 
certolizumab, rituximab, dupilumab, or 
biosimilar agent (if applicable)
90 days prior to screening through the 
end of study participation (6 months 
for rituximab and demonstration of 
CD19+ B cell presence)
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 SLE Medications
Corticosteroids
Oral corticosteroids > 20 mg prednisone 
equivalent/day
28 days prior to Day 1 through the end 
of study participation
Injectable corticosteroids
14 days prior to Day 1 through the end 
of study participation
Non-biologic 
Immunomodulator
Azathioprine (> 2 mg/kg bodyweight/day or 
200 mg/day, whichever is lower), colchicine, 
cyclosporine, cyclophosphamide, tacrolimus 
(oral or topical), gold salts, leflunomide,
minocycline, MTX > 20 mg/week (subcutaneous 
or oral), mycophenolate, penicillamine, 
sirolimus,  everolimus, temsirolimus, or other 
immunomodulatory/immunosuppressive 
therapies (with the exception of oral 
antimalarials as permitted in Section 5.3.1.1)
28 days prior to Day 1 through the end 
of study participation


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Drug Class
Agents Disallowed
Prohibited Period
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)
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, entospletinib, or other 
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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5.4.
Vaccine Guidelines
Prior to study participation, it is recommended that the subject’s vaccinations be brought up to 
date according to local vaccination standards.
Live or attenuated vaccines (including, but not limited to varicella and inhaled flu vaccine) are 
prohibited within 30 days of Day 1, throughout the study, and for 12 weeks after the last dose of 
study drug.
Subjects should be advised to avoid routine household contact with persons vaccinated with 
live/attenuated vaccine components. General guidelines suggest that a study subject’s exposure
to household contacts should be avoided for the below stated time periods:

Varicella or attenuated typhoid fever vaccination – avoid contact for 4 weeks following 
vaccination

Oral polio vaccination - avoid contact for 6 weeks following vaccination

Attenuated rotavirus vaccine - avoid contact for 10 days following vaccination

Inhaled flu vaccine - avoid contact for 1 week following vaccination
Inactivated vaccines (such as inactivated flu vaccines) should be administered according to local 
vaccination standards whenever medically appropriate; however, there are no available data on 
the concurrent use of filgotinib or GS-9876 and their impact on immune responses following 
vaccination.
5.5.
Accountability for 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 drug returned, along with the initials of 
the person recording the information. Dispensing records will include the initials of the 
person dispensing the study drug or supplies
5.5.1.
Investigational Medicinal Product 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 details regarding 
urine collection procedures will be specified in the Laboratory Manual and Subject Procedures 
Manual.
Subject-reported outcomes will be administered, where available, and should be completed
before any other study procedures. Invasive study procedures such as blood draws should be 
done at the end of a study visit, unless otherwise specified. Investigator 
questionnaires/assessments will be administered, where available, and should be performed prior 
to reviewing subject-reported outcomes for that visit, as much as possible. 
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 35 days prior to randomization (Day 1) to determine eligibility 
for participation in the study. The Screening visit will take two separate days to complete. In 
addition, Screening Day 2 cannot occur earlier than 3 days after Screening Day 1 due to the 
timing of the morning urine voids and the 24 hour urine collection. Additional details regarding 
urine collection procedures will be specified in the Laboratory Manual and Subject Procedures 
Manual.
The following will be performed and documented at Screening:

Obtain written informed consent
 

Obtain medical history, including a copy of the kidney biopsy pathology report with a 
histologic diagnosis of LMN performed within the 36 months prior to Screening. The report 
will be forwarded to the Gilead Medical Monitor for review and confirmation of eligibility 
prior to randomization on Day 1.
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
Review inclusion and exclusion criteria

Height and weight

Complete PE

Obtain urine samples for:
Urinary protein excretion will be determined using 2 consecutive morning voids as well 
as a 24-hour urine collection. 
Urinalysis (with urine microscopy and spot protein-to-creatinine ratio). As contamination 
by menstrual blood may interfere with the primary endpoint, whether or not the patient is
menstruating will be recorded on the CRF; microscopic urine examination will evaluate 
for active urine sediment (any of:  > 5 WBC/hpf [pyuria], > 5 RBC/hpf [hematuria], or 
red cell casts in the absence of infection or other causes). In such circumstances,
investigators may ask patients to return for another screening visit.
Urine biomarker sample

Vital signs

Standard 12-lead ECG

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)
HbA1c and TSH
CRP and ESR
Autoantibody panel and complement levels
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)
HCV RNA VL (if subject is HCV Ab positive)
QuantiFERON® TB Gold in Tube Test (if applicable)
Biomarker Samples (whole blood TBNK biomarker sample, serum and plasma biomarker 
samples, vfPBMC sample, and PAXgene RNA sample)


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
Chest x-ray (if one has not already been obtained within 3 months prior to screening)

Record any serious adverse events and all adverse events related to protocol mandated 
procedures occurring after signing of the consent form

Record any concomitant medication in the medical history
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 35 days after screening 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.
A single retest of screening labs is permitted only if there is reason to believe the retest value will 
be within accepted parameters, or if the initial value was either due to a sample processing error 
or an extenuating circumstance.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all concomitant medication, serious adverse events (SAEs), as well as 
any adverse events related to protocol-mandated procedures on the adverse events case report 
form (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 Adverse Events and Toxicity Management for additional details.
6.2.2.
Day 1 Baseline Assessments
The following will be performed and documented prior to dosing:

Updates to medical history (if applicable)

Review inclusion and exclusion criteria

Weight

Symptom-driven PE 

Obtain urine samples for:
Urinary protein excretion will be determined using 2 consecutive morning voids as well 
as a 24-hour urine collection. All 3 urine samples will be collected prior to Day 1, with 
the 24-hour urine collection as close to the Day 1 visit as possible. 
Urinalysis (with urine microscopy and spot protein-to-creatinine ratio). As contamination 
by menstrual blood may interfere with the primary endpoint, whether or not the patient is 
menstruating will be recorded on the CRF; microscopic urine examination will evaluate 
for active urine sediment (any of:  > 5 WBC/hpf [pyuria], > 5 RBC/hpf [hematuria], or 
red cell casts in the absence of infection or other causes). 


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Urine pregnancy test (for females of childbearing potential)
Urine biomarker sample

SELENA-SLEDAI

BILAG

Patient Global Assessment of Disease activity

Physician Global Assessment of Disease activity

36-Item Short Form Health Survey

Vital signs

Standard 12-lead ECG

Obtain predose blood samples for:
Fasting Clinical Laboratory Tests (hematology, serum chemistry with lipid assessments, 
and coagulation)
CRP and ESR
Quantitative serum immunoglobulin test
Autoantibody panel and complement levels
HCV RNA VL (if subject was HCV Ab positive at Screening)
Biomarker Samples (whole blood TBNK biomarker sample, serum and plasma biomarker 
samples, vfPBMC sample, and PAXgene RNA sample)

Study drug dispensing

Review and record all AEs and concomitant medications
Following the completion of the above assessments, the subject will be randomized and 
administered study drug.  
 
 
 
CCI
CCI


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Amendment 2
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6.3.
Randomization
Subjects may not be randomized until the Gilead Medical Monitor has reviewed the kidney 
biopsy pathology report and has confirmed that a subject is eligible. Upon qualification for the 
study, subjects will be randomized in a 1:1 ratio using a computerized IWRS system. 
For each subject at each visit, the clinic will contact the IWRS system and for the appropriate 
bottle number to be dispensed. The bottle will contain the relevant study drug for the period until 
the next dispensation visit.
Refer to Sections 3.3 and 6.1 for additional details.
6.4.
Week 1 Assessments

Weight

Symptom-driven PE 

Obtain urine samples for:
Urinalysis (with urine microscopy and spot protein-to-creatinine ratio). As contamination 
by menstrual blood may interfere with the primary endpoint, whether or not the patient is 
menstruating will be recorded on the CRF; microscopic urine examination will evaluate 
for active urine sediment (any of:  > 5 WBC/hpf [pyuria], > 5 RBC/hpf [hematuria], or 
red cell casts in the absence of infection or other causes). 
Urine pregnancy test (for females of childbearing potential)

Vital signs

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)
CRP and ESR
HCV RNA VL (if subject was HCV Ab positive at Screening)

Study drug accountability

Review and record all AEs and concomitant medications
6.5.
Weeks 2 through Week 28 Assessments (excluding Week 16)
At Weeks 2, 4, and 20, subjects will be instructed to take their study drug in the clinic as the 
first study procedure prior to any others scheduled for those visits.

Weight

Symptom-driven PE 


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
Obtain urine samples for:
Urinalysis (with urine microscopy and spot protein-to-creatinine ratio). As contamination 
by menstrual blood may interfere with the primary endpoint, whether or not the patient is 
menstruating will be recorded on the CRF; microscopic urine examination will evaluate 
for active urine sediment (any of:  > 5 WBC/hpf [pyuria], > 5 RBC/hpf [hematuria], or 
red cell casts in the absence of infection or other causes). 
Urine pregnancy test (for females of childbearing potential)
Urine biomarker sample (Week 2 only)

SELENA-SLEDAI

Vital signs

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)
CRP and ESR
Quantitative serum immunoglobulin test (Weeks 8 and 24 only)
Autoantibody panel and complement levels (Weeks 2, 4, and 8 only)
HCV RNA VL (if subject was HCV Ab positive at Screening)
Plasma PK samples (Weeks 2, 4, and 20 [at least 30 minutes and up to 3 hours after 
dosing] and anytime at Weeks 8 and 24)
Biomarker Samples (Week 2 only [whole blood TBNK biomarker sample, serum and 
plasma biomarker samples, vfPBMC sample, and PAXgene RNA sample])

Study drug accountability

Study drug dispensing (Weeks 4, 8, 12, 20, 24, and 28 only)

Review and record all AE and concomitant medications
6.6.
Week 16 and Week 32 Assessments
At Weeks 16 and 32 subjects will be instructed to take their study drug after predose assessments 
have been completed (eg, up to 2 hours after PK sample collection). The following will be 
performed and documented prior to dosing:

Weight

Symptom-driven PE 


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
Obtain urine samples for:
For Week 16, subjects will submit 2 consecutive morning urine void samples to the study 
center approximately 7 days prior to the Week 16 visit to test their change in urinary 
protein excretion.  Subjects will also submit a 24-hour urine collection that is collected 
immediately prior to the Week 16 visit, or as close to the Week 16 visit as possible. 
These results will inform their treatment assignment for the additional 16 weeks.
For Week 32, subjects will submit 2 consecutive morning urine void samples to the study 
center approximately 7 days prior to the Week 32 visit to test their change in urinary 
protein excretion.  Subjects will also submit a 24-hour urine collection that is collected 
immediately prior to the Week 32 visit, or as close to the Week 32 visit as possible. 
These results will inform their treatment assignment for the additional 20 weeks in the 
Extended Blinded Treatment Phase.
Urinalysis (with urine microscopy and spot protein-to-creatinine ratio). As contamination 
by menstrual blood may interfere with the primary endpoint, whether or not the patient is 
menstruating will be recorded on the CRF; microscopic urine examination will evaluate 
for active urine sediment (any of:  > 5 WBC/hpf [pyuria], > 5 RBC/hpf [hematuria], or 
red cell casts in the absence of infection or other causes). 
Urine pregnancy test (for females of childbearing potential)
Urine PK sample (Week 16 only)
Urine biomarker sample

SELENA-SLEDAI

BILAG

Patient Global Assessment of Disease activity

Physician Global Assessment of Disease activity

36-Item Short Form Health Survey

Vital signs

Standard 12-lead ECG

Obtain predose blood samples for:
Fasting Clinical Laboratory Tests (hematology, serum chemistry with lipid assessments, 
and coagulation)
CRP and ESR


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Autoantibody panel and complement levels
HCV RNA VL (if subject was HCV Ab positive at Screening)
Plasma PK sample (within 2 hours prior to dosing)
Biomarker Samples (whole blood TBNK biomarker sample, serum and plasma biomarker 
samples, vfPBMC sample, and PAXgene RNA sample)

Study drug accountability

Study drug dispensing

Review and record all AEs and concomitant medications
6.7.
Week 36 through Week 48 Assessments

Weight

Symptom-driven PE 

Obtain urine samples for:
Urinalysis (with urine microscopy and spot protein-to-creatinine ratio). As contamination 
by menstrual blood may interfere with the primary endpoint, whether or not the patient is 
menstruating will be recorded on the CRF; microscopic urine examination will evaluate 
for active urine sediment (any of:  > 5 WBC/hpf [pyuria], > 5 RBC/hpf [hematuria], or 
red cell casts in the absence of infection or other causes). 
Urine pregnancy test (for females of childbearing potential)

SELENA-SLEDAI

Vital signs

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)
CRP and ESR
Quantitative serum immunoglobulin test (Week 48 only)
HCV RNA VL (if subject was HCV Ab positive at Screening)

Study drug accountability


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
Study drug dispensing

Review and record all AEs and concomitant medications
6.8.
Week 52 Assessments

Weight

Symptom-driven PE 

Obtain urine samples for:
Morning voids and 24-hour Urine Collection for Urine Protein. Urine samples from 
3 consecutive days will be collected to evaluate urine protein, including morning voids 
during 2 consecutive days prior to each 24-hour urine collection (on the 3rd consecutive 
day).
Urinalysis (with urine microscopy and spot protein-to-creatinine ratio). As contamination 
by menstrual blood may interfere with the primary endpoint, whether or not the patient is 
menstruating will be recorded on the CRF; microscopic urine examination will evaluate 
for active urine sediment (any of:  > 5 WBC/hpf [pyuria], > 5 RBC/hpf [hematuria], or 
red cell casts in the absence of infection or other causes). 
Urine pregnancy test (for females of childbearing potential)
Urine biomarker sample

SELENA-SLEDAI

BILAG

Patient Global Assessment of Disease activity

Physician Global Assessment of Disease activity

36-Item Short Form Health Survey

Vital signs

Standard 12-lead ECG

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)
CRP and ESR


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Autoantibody panel and complement levels
HCV RNA VL (if subject was HCV Ab positive at Screening)
Biomarker Samples (whole blood TBNK biomarker sample, serum and plasma biomarker 
samples, vfPBMC sample, and PAXgene RNA sample)

Study drug accountability

Review and record all AEs and concomitant medications
6.9.
Early Termination Assessments 
All subjects who received at least one dose of study drug and discontinue the study early will 
have the below assessments completed at the time of study discontinuation:

Weight

Complete PE 

Obtain urine samples for:
Urine pregnancy test (for females of childbearing potential)
Urine biomarker sample

Vital signs

Standard 12-lead ECG

Obtain blood samples for:
Clinical Laboratory Tests (hematology, serum chemistry, and coagulation)
CRP and ESR
Autoantibody panel and complement levels
HCV RNA VL (if subject was HCV Ab positive at Screening)
Biomarker Samples (whole blood TBNK biomarker sample, serum and plasma biomarker 
samples, vfPBMC sample, and PAXgene RNA sample)

Study drug accountability

Review and record all AEs and concomitant medications


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6.10.
Final Follow-Up Assessments (4 Weeks Post Treatment)
The following procedures will be completed 4 weeks (± 5 days) after the subject’s last dose of 
study drug.  Subjects that discontinue early from the study will be required to complete the FU 
visit.

Weight

Complete PE 

Obtain urine samples for:
Morning voids and 24-hour Urine Collection for Urine Protein. Urine samples from 
3 consecutive days will be collected to evaluate urine protein, including morning voids 
during 2 consecutive days prior to each 24-hour urine collection (on the 3rd consecutive 
day).
Urine pregnancy test (for females of childbearing potential)
Urine biomarker sample

SELENA-SLEDAI

BILAG

Patient Global Assessment of Disease activity

Physician Global Assessment of Disease activity

36-Item Short Form Health Survey

Vital signs

Obtain blood samples for:
Fasting Clinical Laboratory Tests (hematology, serum chemistry with lipid assessments, 
and coagulation)
CRP and ESR
Autoantibody panel and complement levels
HCV RNA VL (if subject was HCV Ab positive at Screening)
Biomarker Samples (whole blood TBNK biomarker sample, serum and plasma biomarker 
samples, vfPBMC sample, and PAXgene RNA sample)

Review and record all AEs and concomitant medications


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6.11.
Unscheduled Visit (exacerbation of LMN) 
The following procedures will be completed at an unscheduled visit for exacerbation of LMN
(worsening of proteinuria, and/or decrease in eGFR):

Symptom-driven PE 

Obtain urine samples for:
Urinalysis (with urine microscopy and spot protein-to-creatinine ratio). As contamination 
by menstrual blood may interfere with the primary endpoint, whether or not the patient is 
menstruating will be recorded on the CRF; microscopic urine examination will evaluate 
for active urine sediment (any of:  > 5 WBC/hpf [pyuria], > 5 RBC/hpf [hematuria], or 
red cell casts in the absence of infection or other causes). 
Urine pregnancy test (for females of childbearing potential)

Vital signs

Review and record all AEs and concomitant medications
6.12.
Study Assessments
6.12.1.
Priority of Assessments
Subject-reported outcomes will be administered, where available, and are recommended to be 
completed before any other study procedures. Invasive study procedures such as blood draws 
should be done at the end of a study visit, unless otherwise specified. Investigator 
questionnaires/assessments will be administered, where available, and should be performed prior 
to reviewing subject-reported outcomes for that visit, as much as possible. 
6.12.2.
Efficacy
Efficacy assessments will be performed at the time points indicated in the study procedures table 
(Appendix 2). 
6.12.2.1.
Urine Protein Excretion
Several methods exist to assess urine protein excretion. Measurement of protein excretion in a 
24-hour collection period has been the longstanding “gold standard” for the quantitative
evaluation of proteinuria, and will be used to assess the primary outcome. An alternative method 
for quantitative evaluation of proteinuria is measurement of the ratio of protein to creatinine in 
an untimed “spot” urine specimen (UPCR). These ratios correct for variations in urinary 
concentration due to hydration and provide a more convenient method of assessing protein and 
albumin excretion than those requiring timed urine collections, and will be used to provide a 
preliminary assessment of response prior to the Week 16 and Week 32 visits.


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6.12.2.2.
Safety of Estrogens in Lupus Erythematosus National Assessment -Systemic Lupus 
Erythematosus Activity Index (SELENA-SLEDAI)
The SELENA-SLEDAI is an index of SLE flares commonly used in clinical trials as an 
assessment tool of SLE activity with scores that range from 0 to 105, with higher scores 
indicating more severe disease activity.
6.12.2.3.
British Isles Lupus Activity Group (BILAG) Index
The BILAG is an index of SLE flares commonly used in clinical trials as an organ-specific 
assessment tool of SLE activity that includes a 97-question assessment based upon the evaluating 
physician’s intent to treat, which requires an assessment of improved (1), the same (2), worse 
(3), or new (4) over the last month.  Within each of 8 organ systems, multiple manifestations and 
laboratory tests are combined into a single score for that organ that range from A through E, with 
A representing very active disease and E indicating that the organ was never involved.
6.12.2.4.
Physician’s Global Assessments of Disease Activity
The Physician’s Global Assessment of Disease Activity will be recorded on a 0 to 100 mm visual 
analogue scale (VAS; Appendix 9), with 0 indicating “no LMN disease activity” and 
100 indicating “maximum LMN disease activity”. It represents the average assessment of a 
patient's disease activity based on physical examination and laboratory data according to the 
evaluating physician. 
6.12.2.5.
Patient’s Global Assessments of Disease Activity
The Patient Global Assessment reflects the patient's perceived overall health and disease activity, 
with disease activity estimated on a 0 to 100 mm visual analog scale.
6.12.2.6.
36-Item Short Form (SF) Healthy Survey (SF-36)
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).

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.


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6.12.3.
Safety 
Safety will be assessed via AEs, concomitant medications, physical examinations (complete and 
symptom-driven), vital signs, ECGs, and clinical laboratory results.
6.12.4.
Clinical Laboratory Evaluations
All 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. 
Subjects only need to be fasted on days were lipid profiling is scheduled. 

Refer to Appendix 6 for table of clinical laboratory tests.
The laboratory values outside the normal range will be flagged and clinical relevance will be 
assessed by the investigator. More frequent sampling as well as additional tests may be 
performed as deemed necessary by the investigator as indicated. 
Note that in the case where clinically significant laboratory test results are a potential reason for 
discontinuation from the study drug and withdrawal from the study, retesting of the affected 
parameter(s) should be prompt (within 3 to 7 days) after the investigator has consulted with the 
medical monitor. A decision regarding subject discontinuation should be made after the results 
from the retest are available (see Section 3.5 for additional information).
The details of sample handling and shipment instructions will be provided in a separate 
Laboratory Manual.  
6.12.5.
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.
6.12.6.
Physical Examination
A physical examination should be performed at the time points indicated in the study procedures 
table Appendix 2. Any changes from baseline will be recorded. Height will be measured at 
screening only. Subjects should be instructed to remove shoes prior to measurement of height.
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At Screening, a complete physical examination will be performed. A complete physical 
examination should 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.
6.12.7.
Other Safety Assessments
6.12.7.1.
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.
6.13.
Pharmacokinetics Assessments
Blood samples will be collected for plasma PK analysis of filgotinib and its active metabolite 
GS-829845, and GS-9876 post dose at Weeks 2, 4, and 20 (at least 30 minutes and up to 3 hours 
after dosing), anytime at Weeks 8 and 24, and within 2 hours prior to dosing at Weeks 16 and 32.
Urine PK analyses may be performed for filgotinib and its active metabolite GS-829845, and 
GS-9876, using the 24-hour urine collection at Week 16.
6.14.
Biomarker Assessments
Urine samples will be collected for biomarker assessments at Screening, Day 1 (predose), 
Weeks 2, 16, 32, 52, ET, and at the Final FU.  
Blood samples for biomarker assessments (whole blood TBNK biomarker, serum and plasma 
biomarkers, vfPBMC, and PAXgene RNA) will be collected at Screening, Day 1 (predose), 
Weeks 2, 16, 32, 52, ET, and at the Final FU.  
 
 
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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)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
CRF.
7.1.2.
Serious Adverse Events
A 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 IMP 
treatment using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the IMP. For SAEs, an 
alternative causality must be provided (eg, pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting. 
The relationship to study procedures (eg, invasive procedures such as venipuncture) 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 CTCAE, version 4.03. For each episode, 
the highest grade attained should be reported. 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.
If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: 
Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening) or 
Grade 5 (fatal) to describe the maximum intensity of the adverse event. For purposes of 
consistency with the CTCAE, these intensity grades are defined in Table 7-1 and Appendix 4.
Table 7-1.
Grading of Adverse Event Severity
Grade
Adjective
Description
Grade 1
Mild
Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
Grade 2
Moderate
Local or noninvasive intervention indicated; limiting age-appropriate instrumental 
ADL 
Grade 3
Severe
Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL 
Grade 4
Life-threatening
Urgent intervention indicated 
Grade 5
Death 
Death related AE 
*
Activities of Daily Living (ADL) Instrumental ADL refer to opening preparing meals, shopping for groceries or clothes, 
using the telephone, managing money, etc. 
**
Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (CRF/eCRF): all SAEs and adverse events related to 
protocol-mandated procedures.
Adverse Events
Following initiation of study medication, all AEs, regardless of cause or relationship, until 
30-days after last administration of study drug(s) must be reported to the CRF/eCRF database as 
instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
period.


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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 
CRF/eCRF database and Gilead Pharmacovigilance and Epidemiology (PVE) 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(s), 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(s), he/she should promptly 
document and report the event to Gilead PVE.

All AEs and SAEs will be recorded in the CRF/eCRF database within the timelines outlined 
in the CRF/eCRF completion guideline. 
Electronic Serious Adverse Event (eSAE) Reporting Process

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead PVE 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 PVE:
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.
PPD
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
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 CRF/eCRF and the event description section of the SAE 
form.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, 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 suspected unexpected serious adverse reactions (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 investigator’s brochure. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy. 
7.5.
Clinical Laboratory Abnormalities
Laboratory abnormalities are usually not recorded as AEs or SAEs. However, laboratory 
abnormalities (eg, clinical chemistry, hematology, coagulation, and urinalysis) independent of 
the underlying medical condition that require medical or surgical intervention or lead to 
investigational medicinal product interruption or discontinuation must be recorded as an AE, as 
well as an SAE, if applicable. In addition, laboratory or other abnormal assessments 
(eg, electrocardiogram, 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 Common Terminology Criteria for 
Adverse Events (CTCAE) and Laboratory Abnormalities. For AEs associated with laboratory 
abnormalities, the event should be graded on the basis of the clinical severity in the context of 
the underlying conditions; this may or may not be in agreement with the grading of the 
laboratory abnormality.


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7.6.
Toxicity Management 
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3 and as outlined below.
For study-specific interruption and discontinuation criteria, refer to Section 3.5. Specific toxicity 
discontinuation criteria in Section 3.5 supersede below general toxicity guidelines, and in 
general, where discrepancy is present, the more conservative criteria apply.
The Gilead Medical Monitor should be consulted prior to study drug discontinuation when 
medically feasible.
7.6.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
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.
Grades 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 a Grade 3 clinically significant laboratory abnormality or clinical event, IMP may be 
continued if the event is considered to be unrelated to IMP.

For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by 
repeat testing, that is considered to be related to IMP, IMP should be withheld until the 
toxicity returns to ≤ Grade 2.

If a laboratory abnormality recurs to ≥ Grade 3 following re-challenge with IMP and is 
considered related to IMP, then IMP should be permanently discontinued and the subject 
managed according to local clinical practice. Recurrence of laboratory abnormalities 
considered unrelated to IMP may not require permanent discontinuation and study drug may 
be continued at the discretion of the investigator.
7.6.3.
Grades 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 
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.


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
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 will 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 must be monitored 
periodically until symptoms subside, any abnormal laboratory values have resolved or returned 
to baseline levels or they are considered irreversible, or until there is a satisfactory explanation 
for the changes observed.
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 AEs associated with product complaints, occupational exposure with an AE, pregnancy 
reports (regardless of an associated AE), and an AE in an infant following potential exposure 
from breastfeeding.
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).


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Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.  
Occupational exposure is defined as exposure to a medicinal product as a result of one's 
professional or non-professional occupation.  
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 medication and throughout the study, including the post study drug follow-up 
period, to Gilead PVE the pregnancy report form within 24 hours of becoming aware of the 
pregnancy.
Refer to Section 7.3 and the CRF/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 
Sections 7.1.1 and 7.1.2. Furthermore, any SAE occurring as an adverse pregnancy outcome 
post study must be reported to Gilead PVE.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead 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 PVE. Gilead PVE contact information is as follows: 
Email:
 and Fax: 
 
Pregnancies of female partners of male study subjects exposed to study drugs must also be 
reported and relevant information should be submitted to Gilead PVE using the pregnancy and 
pregnancy outcome forms within 24 hours. Monitoring of the pregnancy should continue until its 
conclusion. If the end of the pregnancy occurs after the study has been completed, the outcome 
should be reported directly to Gilead PVE, fax number 
 or email 
 
Refer to Appendix 5 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
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7.7.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead PVE within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP 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.
Refer to Section 7.3 and the CRF/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 CRF/eCRF and/or the SAE report form. Details of the symptoms 
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8.
STATISTICAL CONSIDERATIONS
Efficacy and safety data collected up to Week 16 will be summarized by treatment group for all 
subjects. Data from subjects who do not switch treatment will be summarized for the duration of 
the study by treatment group. Summaries by the combinations of treatment groups may be 
provided, if applicable.
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective is:

To evaluate the efficacy of filgotinib and GS-9876 in subjects with LMN
The secondary objectives are: 

To evaluate the safety and tolerability of filgotinib and GS-9876 in subjects with LMN

To evaluate the PK of filgotinib and GS-9876 in subjects with LMN
The exploratory objectives are: 
 
 
8.1.2.
Primary Endpoint
The primary endpoint is the percent change in urine protein from Baseline (Day 1) to Week 16. 
Urine protein is assessed by urinary protein excretion during a 24-hour urine collection. 
8.1.3.
Secondary Endpoints

Change from Baseline (Day 1) in urine protein (assessed by urine protein excretion during a 
24-hour urine collection) at Week 16

Change from Baseline (Day 1) in eGFR at Week 16

Change from Baseline (Day 1) in UPCR (assessed by urine protein excretion during a 
24-hour urine collection) at Week 16
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
Proportion of subjects with partial remission (defined as urine protein excretion below 
< 3 g/d and urine protein excretion decrease by ≥ 50% among subjects with Baseline (Day 1) 
nephrotic range proteinuria [urine protein excretion ≥ 3 g/d]; or urine protein excretion 
decrease by ≥ 50% among subjects with subnephrotic range proteinuria [urine protein 
excretion < 3 g/d]) at Week 16

Proportion of subjects with complete remission (defined as urine protein excretion below 
0.5 g/day, with no hematuria) at Week 16
8.1.4.
Exploratory Endpoints
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 protein excretion below 
0.5 g/day, with no hematuria) at each visit other than Week 16
8.1.5.
Biomarker Endpoints

Change in JAK-STAT-, SYK-, and disease-related biomarkers in peripheral blood and urine

Association of changes in peripheral blood and urine biomarkers with clinical outcomes

Association of Baseline markers with disease severity and response to filgotinib and 
GS-9876
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.
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. All data collected during treatment plus 
30 days after the last dose of study drug will be included in the safety summaries.
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 non-missing PK concentration data for GS-9876, 
filgotinib or their metabolites. 
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8.2.1.5.
Biomarkers 
The primary analysis set for biomarker analyses will be the Biomarker Analysis Set, which
includes all subjects in the Safety Analysis Set who have at least one evaluable measurement
available at any time point for a given biomarker 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. BLQ 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 measurements will be summarized using standard descriptive 
statistics including sample size, mean, SD, median, Q1, Q3, minimum, and maximum for 
continuous variables and number and percentages of subjects for categorical variables.
Demographic summaries will include sex, race/ethnicity, and age.
Baseline characteristics will include and not limited to a range of proteinuria (< 3g/d, >= 3g/d), 
histologic diagnosis, prior and current treatment for lupus membranous nephropathy, and 
patient-reported and physician-reported outcome assessments.
8.5.
Efficacy Analysis 
Details of the efficacy analyses will be described in the Statistical Analysis Plan (SAP).
8.5.1.
Primary Analysis
The primary endpoint, the percent change from Baseline (Day 1) in 24-hour proteinuria at 
Week 16, will be calculated and the 95% confidence interval will be constructed for each 
treatment group. 
8.5.2.
Secondary Analyses
All continuous secondary 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 group. All categorical secondary endpoints will be summarized by the number and 
percentage of subjects who meet the endpoint definition. The 95% CI will be provided, as 
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8.5.3.
Exploratory Analyses
 
8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set.  Safety will be evaluated by 
the 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 drug + 30 days will be included in the safety analysis.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug 
administration page of the eCRF. 
Duration of exposure to study drug will be summarized as the number of weeks between the 
first and last dose of the study drug, inclusive, regardless of temporary interruptions in study 
drug administration.
8.6.2.
Adverse Events
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). System Organ Class (SOC), High-Level Group Term (HLGT), 
High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be attached to 
the clinical database.
Treatment-emergent adverse events (TEAEs) are defined as one or both of the following:

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.
Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC, 
and PT) will be provided. TEAEs will also be summarized by relationship to study drug and 
severity. 
All observed AEs will be presented in by-subject listings.
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8.6.3.
Laboratory Evaluations
Selected laboratory data will be summarized (n, mean, SD, median, Q1, Q3, minimum, and 
maximum) along with corresponding changes. The incidence of treatment-emergent graded 
laboratory abnormalities will be summarized similarly.
Graded laboratory abnormalities will be defined using CTCAE 4.03 grading scale in Appendix 4.
Laboratory abnormalities that occur before the first dose of study drug or after the subject has 
been discontinued from treatment for at least 30 days will be included in a data listing.
8.6.4.
Other Safety Evaluations
Individual data for physical examination findings, prior and concomitant medications and
medical history will be provided. Vital signs measurements will be listed by subject and 
summarized by incidence of events/abnormalities or descriptive statistics as appropriate.
8.7.
Pharmacokinetic Analysis
Plasma concentrations and other PK parameters of filgotinib, the active metabolite of filgotinib 
(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 other filgotinib or GS-9876 metabolite(s) 
may also be determined and analyzed.
Urine PK analyses may be performed for GS-9876, filgotinib and its active metabolite, 
GS-829845, using the 24h urine collection at Week 16.
8.8.
Biomarker Analysis
 
 
 
 
 
 
For biomarker analysis, 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 changes, as appropriate.
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Biomarker objectives may be further described and updated based on evolving scientific 
knowledge of filgotinib and GS-9876.
 
 
8.9.
Sample Size
The sample size was chosen based on the practical considerations and to ensure that a clinically 
meaningful reduction in proteinuria from Baseline (Day 1) could be detected in any of the 
treatment groups, filgotinib or GS-9876.  With 16 subjects per treatment group (32 subjects 
total), there is a 80%  power to detect a 35% reduction from Baseline (Day 1) in proteinuria at 
Week 16 with a standard deviation of 50% and a 2-sided 0.05 significance level.
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 recommendation to Gilead whether the nature, frequency, and 
severity of adverse effects associated with study treatment warrant the early termination of the 
study in the best interests of the participants, whether the study should continue as planned, or 
the study should continue with modifications.
The first DMC data review meeting will be conducted after approximately 50% of planned 
subjects enroll and complete through 16 weeks of study treatment. 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 and secondary analyses will be conducted after all subjects either complete their
Week 16 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.
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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. The investigator will not begin any study subject activities until 
approval from the IRB 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 any modifications made to the protocol or any accompanying material to be provided to 
the subject after initial IRB 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-approved consent form for documenting written 
informed consent. Each informed consent (or assent as applicable) will be appropriately signed 
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conducting the consent discussion, and also by an impartial witness if required by IRB 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, 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, CRF/eCRF, the IMP, and any other study information, 
remain the sole and exclusive property of Gilead during the conduct of the study and thereafter. 
This information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, CRF and query forms, IRB 
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 will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data.  The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility have been received.  Subsequent to data entry, a study monitor will perform source 
data verification within the EDC system. Original entries as well as any changes to data fields 
will be stored in the audit trail of the system.  Prior to database lock (or any interim time points 


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as described in the clinical data management plan), the investigator will use his/her log in 
credentials to confirm that the forms have been reviewed, and that the entries accurately reflect 
the information in the source documents. The eCRF capture the data required per the protocol 
schedule of events and procedures. System-generated or manual queries will be issued to the 
investigative site staff as data discrepancies are identified by the monitor or internal Gilead staff, 
who routinely review the data for completeness, correctness, and consistency. The site 
coordinator is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (e.g. data entry error). At the conclusion of the trial, Gilead will provide the site 
with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Where possible, IMP should be destroyed at the site. At the start of the study, the study monitor 
will evaluate each study center’s IMP disposal procedures and provide appropriate instruction for 
disposal or return of unused IMP supplies. If the site has an appropriate standard operating 
procedure (SOP) for drug destruction as determined by Gilead Sciences, the site may destroy 
used (empty or partially empty) and unused IMP supplies as long as performed in accordance 
with the site’s SOP. This can occur only after the study monitor has performed drug 
accountability during an on-site monitoring visit. 
A copy of the site’s IMP Disposal SOP or written procedure (signed and dated by the 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 IRBs 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 in 
accordance with local requirements and receive documented IRB 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, e.g. 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 
CRF/eCRF.
The monitor is responsible for routine review of the CRF/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 CRF/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
Austin HA, 3rd, Illei GG, Braun MJ, Balow JE. Randomized, controlled trial of prednisone, 
cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am 
Soc Nephrol 2009;20 (4):901-11.
Bachelez H, van de Kerkhof PC, Strohal R, Kubanov A, Valenzuela F, Lee JH, et al. Tofacitinib 
versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a 
phase 3 randomised non-inferiority trial. Lancet 2015;386 (9993):552-61.
Bahjat FR, Pine PR, Reitsma A, Cassafer G, Baluom M, Grillo S, et al. An orally bioavailable 
spleen tyrosine kinase inhibitor delays disease progression and prolongs survival 
in murine lupus. Arthritis Rheum 2008;58 (5):1433-44.
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Amendment 2
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Amendment 2
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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, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 6.
Clinical Laboratory Assessment Table
Appendix 7.
Safety of Estrogens in Lupus Erythematosus National Assessment trial-based 
Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)
Appendix 8.
British Isles Lupus Activity Group (BILAG) Index
Appendix 9.
Physician’s Global Assessment of Disease Activity
Appendix 10.
Patient Global Assessment of Disease Activity
Appendix 11.
36-Item Short Form Health Survey


PPD
PPD
PPD
GS-98 7 6/F ilgotinib 
Protocol GS-US-437-4093 
Final 
Gilead Sciences, Inc. 
Amendment 2 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNU\VLEDGEMENT 
A Phase 2, Randomized, Double-Blind, Multicenter Study Evaluating the Safety and Efficacy of 
Filgotinib and GS-9876 in Subjects with Lupus Membranous Nephropathy (LMN) 
GS-US-437-4093, AMENDMENT 2, 21 MARCH 2018 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
_____ (Printed) 
Study Director and Medical Monitor 
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 
infonnation provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator ame (Printed) 
Signature 
Date 
Site Number 
CONFIDE TIAL 
Page 98 
21 March 2018 


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Appendix 2.
Study Procedures Table
Visit Window (Days)
Blinded Treatment Phase
Extended Blinded 
Treatment Phase
End of 
Study
Unscheduled 
Visit 
(exacerbation 
of LMN)f
Screena
D1/
Baseline
Week 
1
Weeks 2, 4, 8, 12, 
18, 20, 24, 28
Week 
16b
Week 
32c
Weeks 36,
40, 44, 48
Week
52
F/Ud
ETe
-35
0
±3
±3
±3
±3
±5
±5
±5
±5
Written Informed 
Consent
X
Medical History, 
including kidney biopsy 
report
X
Review 
Inclusion/Exclusion 
Criteria
X
X
Randomization
X
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
Complete Physical 
Examination
X
X
X
Symptom-driven 
Physical Examinationg
X
X
X
X
X
X
X
X
2 Morning voids &
24-hour Urine Collectionh
Xh
Xh
Xh
Xh
Xh
Xh
Urinalysisi
X
X
X
X
X
X
X
X
X
SELENA-SLEDAI j, bb
X
X
X
X
X
X
X
BILAG k, bb
X
X
X
X
X


GS-9876/Filgotinib
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Amendment 2
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Visit Window (Days)
Blinded Treatment Phase
Extended Blinded 
Treatment Phase
End of 
Study
Unscheduled 
Visit 
(exacerbation 
of LMN)f
Screena
D1/
Baseline
Week 
1
Weeks 2, 4, 8, 12, 
18, 20, 24, 28
Week 
16b
Week 
32c
Weeks 36,
40, 44, 48
Week
52
F/Ud
ETe
-35
0
±3
±3
±3
±3
±5
±5
±5
±5
Patient Global 
Assessment of disease 
activityl, bb
X
X
X
X
X
Physician Global 
Assessment of disease 
activitym, bb
X
X
X
X
X
36-Item Short Form 
Health Survey bb
X
X
X
X
X
Vital Signsn
X
X
X
X
X
X
X
X
X
X
X
ECG
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
Serum Chemistry
X
X
X
X
X
X
X
X
X
X
Fasting Lipids
X
X
X
X
Coagulation
X
X
X
X
X
X
X
X
X
X
HbA1c and TSH
X
CRP and ESR
X
X
X
X
X
X
X
X
X
X
Quantitative Serum 
Immunoglobulin Test
X
Xcc
Xdd
Autoantibody Panel & 
Complement Levels
X
X
Xz
X
X
X
X
X
Serum Pregnancy Testo
X
Urine Pregnancy Testo, p
X
X
X
X
X
X
X
X
X
X


GS-9876/Filgotinib
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Gilead Sciences, Inc. 
Amendment 2
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Visit Window (Days)
Blinded Treatment Phase
Extended Blinded 
Treatment Phase
End of 
Study
Unscheduled 
Visit 
(exacerbation 
of LMN)f
Screena
D1/
Baseline
Week 
1
Weeks 2, 4, 8, 12, 
18, 20, 24, 28
Week 
16b
Week 
32c
Weeks 36,
40, 44, 48
Week
52
F/Ud
ETe
-35
0
±3
±3
±3
±3
±5
±5
±5
±5
FSH Testq
X
HIV-1/2, HBV, HCV 
Serology
X
HCV RNA VLr
X
X
X
X
X
X
X
X
X
X
QuantiFERON® TB 
Gold in Tube Tests
X
Chest X-Rays
X
Plasma PK Samplet
X
X
X
Urine PK Samplesu
X
Whole Blood TBNK 
Biomarker Sample
X
X
Xx
X
X
X
X
X
Serum Biomarker 
Sample
X
X
Xx
X
X
X
X
X
Plasma Biomarker 
Sample
X
X
Xx
X
X
X
X
X
vfPBMC Sample
X
X
Xx
X
X
X
X
X
PAXgene RNA Sample
X
X
Xx
X
X
X
X
X
CCI


GS-9876/Filgotinib
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Final
Gilead Sciences, Inc. 
Amendment 2
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Visit Window (Days)
Blinded Treatment Phase
Extended Blinded 
Treatment Phase
End of 
Study
Unscheduled 
Visit 
(exacerbation 
of LMN)f
Screena
D1/
Baseline
Week 
1
Weeks 2, 4, 8, 12, 
18, 20, 24, 28
Week 
16b
Week 
32c
Weeks 36,
40, 44, 48
Week
52
F/Ud
ETe
-35
0
±3
±3
±3
±3
±5
±5
±5
±5
Urine Biomarker 
Sample
X
X
Xx
X
X
X
X
X
In-Clinic Study Drug 
Administrationy
X
X
X
X
Study Drug 
Accountability
X
X
X
X
X
X
X
Study Drug Dispensing
X
Xaa
X
X
X
Review AEs & 
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
a
Prospective subjects should be screened no more than 35 days prior to the administration of the first dose of study treatment. The Screening visit will take two separate days to 
complete. In addition, Screening Day 2 cannot occur earlier than 3 days after Screening Day 1 due to the timing of the morning urine voids and the 24 hour urine collection. 
b
Urinary protein excretion will be determined using 2 methods – 2 consecutive morning voids as well as a 24-hour urine collection. For the Baseline assessment, all 3 urine 
samples will be collected prior to Day 1, with the 24-hour urine collection as close to the Day 1 visit as possible. At Week 16, the primary study endpoint will be assessed by 
urine protein excretion during a 24-hour urine collection. Two consecutive morning voids prior to the Week 16 visit will be used to determine response for subsequent study 
treatment. All subjects who achieve a ≥ 35% reduction in urinary protein excretion (using an average of the UPCR from the morning voids) from Baseline (Day 1) will 
continue to receive their assigned blinded study treatment (filgotinib 200 mg + PTM GS-9876, or GS-9876 30 mg + PTM filgotinib) for an additional 16 weeks. Subjects who 
do not achieve a ≥ 35% reduction in urinary protein excretion from Baseline (Day 1) to Week 16 will switch study treatment for 16 weeks in a blinded fashion (ie, those on 
filgotinib will switch to GS-9876 + PTM filgotinib, while those on GS-9876 will switch to filgotinib + PTM GS-9876)
c
After 32 weeks of blinded treatment, those who have a ≥ 35% reduction in urinary protein excretion (using an average of the UPCR from 2 morning voids) from Day 1
(for subjects who remained on the randomized study treatment after Week 16) or from Week 16 (for subjects who switched treatment at Week 16) will continue their assigned 
blinded treatment for an additional 20 weeks in the Extended Blinded Treatment Phase.  Subjects that do not achieve a ≥ 35% reduction in urinary protein excretion from 
Day 1 (for subjects who remained on the randomized study treatment after Week 16) or from Week 16 (for subjects who switched treatment at Week 16) to Week 32 will be 
allowed to continue whichever treatment led to the greatest reduction in urinary protein excretion (from Day 1 to Week 16 on initial study treatment or from Week 16 to 
Week 32 on switched treatment), or either study treatment per the Investigator’s discretion during the Extended Blinded Treatment Phase.
d
The Follow-up (FU) Visit as detailed in the End of Study section of the Study Procedures Table will be completed 4 weeks after the last dose of study treatment. For subjects 
that complete the entire study, the FU visit will be conducted at Week 56.
e
Subjects who discontinue from the study for any reason will complete the Early Termination (ET) Visit at the time of study discontinuation. 
f
Subjects seen at an unscheduled visit for disease exacerbation (worsening of proteinuria, and/or decrease in eGFR) will complete the Unscheduled Visit assessments.
g
Symptom-driven physical examinations will be performed, as needed, based on reported signs and symptoms.


GS-9876/Filgotinib
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Gilead Sciences, Inc. 
Amendment 2
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h
Urinary protein excretion will be determined using 2 consecutive morning voids as well as a 24-hour urine collection. 
-For the Day 1 assessment, all 3 urine samples will be collected prior to Day 1, with the 24-hour urine collection as close to the Day 1 visit as possible. 
-For Week 16, subjects will submit 2 consecutive morning urine void samples to the study center approximately 7 days prior to the Week 16 visit to test their change in 
urinary protein excretion.  Subjects will also submit a 24-hour urine collection that is collected immediately prior to the Week 16 visit, or as close to the Week 16 visit as 
possible. These results will inform their treatment assignment for the additional 16 weeks.
-For Week 32, subjects will submit 2 consecutive morning urine void samples to the study center approximately 7 days prior to the Week 32 visit to test their change in 
urinary protein excretion.  Subjects will also submit a 24-hour urine collection that is collected immediately prior to the Week 32 visit, or as close to the Week 32 visit as 
possible. These results will inform their treatment assignment for the additional 20 weeks in the Extended Blinded Treatment Phase.
i
The urinalysis will include urine microscopy and spot protein-to-creatinine ratio. As contamination by menstrual blood may interfere with the primary endpoint, whether or 
not the patient is menstruating will be recorded on the CRF; microscopic urine examination will evaluate for active urine sediment (any of:  > 5 WBC/hpf [pyuria], 
> 5 RBC/hpf [hematuria], or red cell casts in the absence of infection or other causes). In such circumstances, investigators may ask patients to return for another screening 
visit.
j
Safety of Estrogens in Lupus Erythematosus National Assessment trial-based SLE Disease Activity Index (SELENA-SLEDAI)
k
British Isles Lupus Activity Group (BILAG) 
l
Patient global assessment of disease activity 
m
Physician global assessment of SLE disease activity 
n
Vital signs include resting blood pressure, respiratory rate, heart rate, and body temperature. 
o
Females of childbearing potential only.
p
If a urine pregnancy test is positive, study drug should be immediately interrupted and the subject should return to the site for a serum pregnancy test to confirm result.
q
Females of nonchildbearing potential only.
r
Subjects with positive HCV Ab, but negative HCV RNA VL at Screening are eligible per investigator judgment, but require ongoing monitoring during the study.
s
Subjects previously treated for latent TB or active TB described in Inclusion # 17 do not need to have the QuantiFERON® TB-Gold In-Tube test (or equivalent assay) 
obtained, but a chest radiograph must be obtained if not done so within 3 months prior to screening (with the report or films available for investigator review). All other 
subjects must have the QuantiFERON® TB-Gold In-Tube test (or equivalent assay) obtained at screening AND a chest radiograph (views as per local guidelines) taken at 
screening or within the 3 months prior to screening (with the report or films available for investigator review).
t
Blood samples will be collected for plasma PK analysis of filgotinib and its active metabolite GS-829845, and GS-9876 post dose at Weeks 2, 4 and 20 (at least 30 minutes 
and up to 3 hours after dosing), anytime at Weeks 8 and 24, and within 2 hours prior to dosing at Weeks 16 and 32.
u
Urine PK analyses will be collected for GS-9876, filgotinib and its active metabolite, GS-829845, using the 24h urine collection at Week 16.
 
 
  
x
Biomarker assessments will be collected at Week 2 only.
y
At Weeks 2, 4, and 20, subjects will be instructed to take their study drug in clinic as the first study procedure prior to any others scheduled for that visit. At Day 1, and 
Weeks 16 and 32, subjects will be instructed to take their study drug after predose assessments have been completed (eg, 2 hours after PK sample collection at Weeks 16 
and 32).
z
Autoantibody panel and complement levels will be collected at Weeks 2, 4, and 8 only.
aa
Study drug will be not be dispensed at Weeks 2 and 18.
bb
Questionnaires will be administered where available.
cc
Quantitative serum immunoglobulin testing will be performed at Week 8 and 24 only.
dd
Quantitative serum immunoglobulin testing will be performed at Week 48 only.
CCII 
I 


GS-9876/Filgotinib
Protocol GS-US-437-4093
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Amendment 2
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Appendix 3.
Management of Clinical and Laboratory Adverse Events
*
Refer to Sections 3.5 and 7.6 for details
Grade 1 
~-Gr-ade-2 _
I 
.___
I _Gr-ade-3 _____.I .___I --G-ra-de 4 _ 
_____, 
May continue 
Repeat lab to 
dosing at the 
confirm toxicity 
discretion of the 
grade 
investigator 
, 
If confirmed and possibly and/or probably related to 
investigational medicinal products: 
1. 
Withhold investigational medicinal products until 
:,; Grade 2 
2. 
Rest.art all investi1rntional medicinal oroducts at full dose 
l 
If Grade 3 or 4 recurrence that is confirmed and possibly or 
probably related to investigational medicinal products, 
discontinue all investigational medicinal products dosing 
oermanentlv 
l 
Repeat lab to 
confirm toxicity 
grade 
l 
If c onfirmed and unrelated to 
estigational medicinal 
inv 
pro 
the 
ducts, dosing may continue at 
discretion of the investigator 
If confirmed and 
possibly or probably 
related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently 
and follow at 
periodic intervals at 
least weekly until a 
return to baseline or 
is otherwise 
explained 
If Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all 
invcstigational medicinal products at the same dose at the 
discretion of the investigator 


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Final
Gilead Sciences, Inc. 
Amendment 2
CONFIDENTIAL
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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 
v4.03
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).


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Final
Gilead Sciences, Inc. 
Amendment 2
CONFIDENTIAL
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Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
The administration of filgotinib in embryo-fetal animal development studies resulted in 
decreased numbers of viable rat fetuses, increased resorptions, and visceral and skeletal 
malformations. Similar effects were noted in the rabbit. A safety margin relative to human 
exposure has not been identified. Therefore, filgotinib is contraindicated during pregnancy.
Relevant non-clinical reproductive toxicity studies of GS-9876 did not have findings that raise a 
strong suspicion for human teratogenicity/fetotoxicity.  There is no data from pregnant women 
who have taken GS-9876.
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 
below criteria for being post-menopausal, are not permanently sterile, or do not have medically 
documented ovarian failure must have pregnancy testing as outlined by the protocol. 
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women < 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 
permanent sterilization.
b) Definition of Male Fertility
For the purposes of this study, a male-born subject is considered fertile after the initiation of 
puberty unless permanently sterile by bilateral orchiectomy or has medical documentation of 
permanent male infertility. Vasectomy is not considered permanent sterilization.


GS-9876/Filgotinib
Protocol GS-US-437-4093
Final
Gilead Sciences, Inc. 
Amendment 2
CONFIDENTIAL
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2) Contraception for Female Subjects
a) Study Drug Effects on Pregnancy and Hormonal Contraception
Filgotinib is contraindicated in pregnancy as there is a possibility of human 
teratogenicity/fetotoxicity in early pregnancy based on non-clinical data. Data from a drug-drug 
interaction study of filgotinib and hormonal contraceptives 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. Relevant non-clinical reproductive toxicity studies 
of GS-9876 did not have findings that raise a strong suspicion for human 
teratogenicity/fetotoxicity. In vitro drug interaction assessment of GS-9876 and hormonal 
contraceptives suggests that there is no clinically relevant effects that would decrease
contraception efficacy. 
For male subjects, male condom should be used; for their female partners of childbearing 
potential, an accepted contraceptive method should also be considered. Details are outlined 
below.
Please refer to the latest version of the IBs for filgotinib and GS-9876 for additional information.
b) Contraception for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. Women 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 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


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Gilead Sciences, Inc. 
Amendment 2
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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)
Or

Female subjects who wish to use a hormonally based method must 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.  Hormonally-based 
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
Hormonal methods (each method must be used with a barrier method, preferably 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 refrain from egg donation and in vitro fertilization during the study 
and until 36 days after the last study drug dose.
3) Contraception Requirements for Male Subjects
It is theoretically possible that a relevant concentration of study drug may be achieved in a 
female partner from exposure to the male subject’s seminal fluid. Therefore, male subjects with 
female partners of childbearing potential must use condoms during study participation and for 
90 days after the last study drug dose. Female partners of male study subjects should consider 
using one of the above methods of contraception as well. Male subjects must also refrain from 
sperm donation during the study and until 90 days after the last dose of study drug.


GS-9876/Filgotinib
Protocol GS-US-437-4093
Final
Gilead Sciences, Inc. 
Amendment 2
CONFIDENTIAL
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4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method (LAM). Female condom and male condom should not be used 
together.
5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 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. Male subjects whose 
partner has become pregnant or suspects she is pregnant during the study or up to 90 days after 
the last dose of study drug are to report the information to the investigator immediately.
Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome are outlined in 
Section 7.7.2.1.
6) Pregnancy Testing
All females of childbearing potential will have urine pregnancy testing every 4 weeks during the 
study. If a positive urine pregnancy test is reported, the female subject should stop all study 
drugs and return to the clinic for a serum pregnancy test.


GS-9876/Filgotinib
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Gilead Sciences, Inc. 
Amendment 2
CONFIDENTIAL
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Appendix 6.
Clinical Laboratory Assessment Table
Hematology
Chemistry
Urine
Other
White blood cell (WBC) 
count
Hematocrit
Hemoglobin
Red blood cell (RBC) 
count
Red blood cell indices
Platelet count
Differentials (absolute 
and percentage), 
including:
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 clearance1
Glucose
Phosphorus
Magnesium
Potassium
Sodium
Creatine Phosphokinase 
(CPK)
Amylase
Lipase
Uric acid (at screening only)
Appearance
Blood
Color
Dipstick
  Glucose
  Specific gravity
  Nitrites
  Leukocyte esterase
  pH
  Protein
  Urobilinogen
Reflex to microscopic 
urinalysis if dipstick result 
is abnormal.
Spot urine protein and 
creatinine (for UPCR)
24-hour urine for protein 
and creatinine
QuantiFERON® TB – Gold 
In-Tube Analysis (if 
required per inclusion 
criteria; at screening only)
FSH (as applicable; at 
screening only)
HbA1c (at screening only)
TSH (at screening only)
C-reactive protein (CRP) 
Erythrocyte sedimentation 
rate (ESR)
Quantitative 
immunoglobulins (IgG, 
IgM, and IgA)
Autoantibody panel (ANA2
with reflex ENA3 [dsDNA4, 
Sm5, RNP6, SSA, and 
SSB])
Complement levels (C3, 
C4, and CH50)
Virology
Hepatitis B surface antigen 
(HBsAg)
Hepatitis B virus (HBV) 
core antibody
HBV DNA (reflex)
Hepatitis C Virus (HCV) 
Ab (if positive, then reflex 
HCV RNA)
HCV Viral Load (if 
applicable)
Human immunodeficiency 
virus 1 and 2 Ab
Coagulation
Fasting Lipids
Pregnancy
Activated partial 
thromboplastin time 
(aPTT)
Prothrombin time 
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
Estimated glomerular filtration rate based on the MDRD formulation (eGFRMDRD)
ANA = antinuclear antibody 
ENA = extractable nuclear antigen 
dsDNA = double stranded DNA
Sm = Smith antigen
RNP =  ribonucleoprotein 


GS-9876/Filgotinib
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Amendment 2
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Appendix 7.
Safety of Estrogens in Lupus Erythematosus National Assessment 
trial-based Systemic Lupus Erythematosus Disease Activity Index
(SELENA-SLEDAI)
Hybrid SELENA SLEDAI with SELENA SLEDAI FLARE INDEX and PGA 
(Circle in SLE':DAI Score column if descriptor is present at the lime of the visit or in the preceding 4 weeks) 
Item 
Check 
Score 
Descriptor 
Definition 
no. 
if active 
1 
8 
Seizure 
Recent onset, exclude metabolic, infectious or drug causes 
2 
8 
Psychosis 
Altered ability to function in normal activity due to severe disturbance in the 
perception of rea lity. Include hallucinations, incoherence, marked loose 
associations, impoverished thought content, marked illogical thinking, bizarre, 
disorganized, or catatonic behavior. Exclude uremia and drug causes 
3 
8 
Organic 
Altered mental function with impaired orientation, memory, or other intellectual 
brain 
function, with rapid onset and fluctuating clinical features, inability to sustain 
syndrome 
attention to environment, plus at least 2 of the following: perceptual 
disturbance, incoherent speech, insomnia or daytime drowsiness, increased or 
decreased psychomotor activity. Exclude metabolic, infectious or drug causes 
4 
8 
Visual 
Retinal changes of SLE. Include cytoid bodies, retinal hemorrhages, serous 
disturbance 
exudates or hemorrhages in the choroid, or optic neuritis, scleritis or 
episcleritis. Exclude hypertension, infection, or drug causes 
5 
8 
Cranial nerve New onset of sensory or motor neuropathy involving cranial nerves 
disorder 
6 
8 
Lupus 
Severe, persistent headache; may be migrainous, but must be nonresponsive 
headache 
to narcotic analgesia THIS WOULD RARELY BE ATTRIBUTED TO 
SLE. .. ALMOST NEVER SCORED 
7 
8 
CVA 
New onset Cerebrovascular accident(s). Exclude arteriosclerosis 
8 
8 
Vasculitis 
Ulceration, gangrene, tender finger nodules, periungual infarction, splinter 
hemorrhages or biopsy or a ngiogram proof of vasculitis 
9 
4 
Arthritis 
> 2 joints with pain and signs of inflammation (Le. tenderness with swelling or 
effusion) 
10 
4 
Myositis 
Proximal muscle achi ng/weakness, associated with elevated creatinine 
phosphokinase (CK)/aldolase, or EMG changes or a biopsy showing myositis 
11 
4 
Urinary casts Heme-granular or RBC casts 
12 
4 
Hematuria 
> 5 RBC/high power field. Exclude stone, infection or other cause 
13 
4 
Proteinuria 
More than 0.5 gm/24 hours. 
14 
4 
Pyuria 
> 5 WBC/high power field. Exclude infection 
15 
2 
Rash 
Inflammatory type rash 
16 
2 
Alopecia 
Abnormal, patchy or diffuse loss of hair 
17 
2 
Mucosal 
Oral or nasal ulcerations 
ulcers 
18 
2 
Pleurisy 
Pleuritic chest pain or pleural rub or effusion, or pleural thickening (does not 
require an objective component if medically convincing) 
19 
2 
Pericarditis 
Classic pericardia! pain and/or rub, effusion or ECG or echocardiogram 
confirmation (does not require an objective component if medically convincing) 
20 
2 
Low 
Decrease in CH50, C3 or C4 < lower limit of nl for testing laboratory 
complement 
21 
2 
Increased 
Increased DNA binding above normal range for testing laboratory 
DNA binding 
22 
1 
Fever 
> 38°C. Exclude infectious cause 
23 
1 
Thrombocyto < 100 x 109 platelets/L, exclude drug causes 
penia 
24 
1 
Leukopenia 
< 3 x 109 WBC/L, exclude drug causes 
Total SCORE 


GS-9876/Filgotinib
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Gilead Sciences, Inc. 
Amendment 2
CONFIDENTIAL
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Appendix 8.
British Isles Lupus Activity Group (BILAG) Index
BILAG2004 INDEX 
Only rKord it 
doc to SU: Diaaa At:Ciritr • 11 
n·ffks (c,ompared mtb the pnrio 
Sccmg: ND ·• DHt 
l 
llllprv . 
2 
Saa 
3 w ... 
4 
Yes/No OR. Vllat (1rUR illdiafM) 
~= 
ir aia.JIIIIL~w..lll.lUllU. 
CONSTTIUITO i\l. 
L P,u!m - clDcmm!ll!d :> 37 .SWC 
Weigbr kiss-
. 
. 
:> ~. 
3. I yrrc,hadf!nnp>dty/5J11moJC!lfl,ltly 
ADlllml 
MUCoct.r'TA.l'\'EOUS 
s. 
· !nlpOIIII - ~ 
Ci. 
• empliaa - Did 
7.~
--
1. ~. 
mild 
9. 
. --
10 
I) PlmlicalmsllJu!klllS 
12 u. 
14. 
15.Alop«ia--
l Alopma-mild 
l .~l!r}'tleD,' 
11.Splim!rhHrwmi!a 
:>TlJROPS\•cmaDJc 
19 A5i!p:ic lll!lringuu 
10. Cermral 
--
ll. Dml) .. 
l2 MJ!lapldly 
23. Am- cmfnSXINJ SD12 
P5ydlom 
25 Aas- in&mrnmry demytlin,uing 
~y 
l6 M~ 
(.siqle'llmlllpla) 
( 
17. Cnmill D!lmlpillhJ 
( 
lS 
( 
29 PalJ"llll!llnl!imhT 
( 
30 Sl'lZ1!R disardff 
( 
31.S 
( 
32 Catbruvasailll disBif (DDt 
ID VtiOilitis) ( 
33. c.o~ dys:6.111,.lian 
( 
34. MCM!lll!llldismla" 
( 
35 Au!anamic clilCIIM 
( 
36 Cm 
. ('ISO 
( 
37 
bsd.lcbe - -
111:Rm:DDII.I: 
( 
31. BeadK.be fnDI ICbJpe1m.sioa 
( 
Ill\mon: 1 
00 
) 
) 
) 
) 
) 
) 
) 
) 
i 
) 
) 
) 
) 
mt miu·s to m:mifi tatio 
oc,cuning m the 1a.aJ. 
CAJIDlORESl'lRATOltY 
44. Myoanfms -mild 
c 
4S. M~-Clnli.acfaillm ( 
46. Amrydm:u 
( 
47. Nrw\~ 
( 
s Pl!miiy,Pl!l1cmfiis 
( 
9. Cardiac. lllllpOnade 
( 
SO. 
( 
SL Pulmmw}' 
( 
s ImmitilJ 
( 
S3Sbrimq 
s)'lllllrtmt 
( 
S-tAmtim 
( 
SS. CGnmlryl 
( 
CASTRO ill:STINAL 
SCi. LDpa.s pem .. 
S7 • .Abdmmml saasins ar Bile5 
SI. Lupas l'llll'rimlmJilu 
S9. MallbsofpliDD 
60. Pracen ming emm,pllhJ 
61. 
]ISl!lldD-obsmlcaaD 
62. LDpas bepmtis 
63 Aau Jupu dio 
64. Aaft Jupupancr&1ilis 
PfHJJWWf 
65. 0ma.l 
~O&is 
66. KIDlil:is-~ 
67. &mlilis • 
Alll!l:i« 
.. 
69. POJlmar ~nlillll 
· !11!11!11! 
0. Posimar muis.ln!in&l 
· · • mild 
71. f.4iisd!rilis 
2. Sdams-smn 
13. Scl.m!is • mild 
4. R.smaltcbamidal-«.CD.11Wclisase 
7S. ho. mean 
J 
(cymid 
· ) 
76. 0pci.t llellliris 
77. Ammar iscllMlmc optic lll'IRpalhy 
RENAL 
~'5tnlir bJoodpm~ (mm Hg) 
\\WI! 
9. 
• b 
prtS5lft (111111 
\'WI' 
80. Aculmt!d lrJpmmsian 
Yes/No ( 
81. Urin! dipmck 
(=I. ++cl.+++=]) ( 
8 UriDI! 
. . aoo 
I( 
u. Urine pm 
mio 
( 
84. 
ham: llllllt pml!!:iD 00 
\'WI! 
( 
85. 
Yesi'No ( 
86. Cretinme {pb!;ma.\sermll) 
pl!IQL1 ( 
87. GfR (w:w.ac 
.131111 ( 
81. .Aai\11! 
!ldimm 
Yes/No ( 
89. Aaiw aepmUis 
Yai'No ( 
JWMAIPLOGlfAL 
90. ~m(g'dl) 
91 Toal 
· cell caam ( 10'11) 
92. 
(1. 10'!1) 
93. LyUljlhKJtes (11: 10 II) 
94. 
('& 10'11) 
95. TIP 
96. E\!idei:n of ldiw 
97. Coombs' es1 posuiw (i 
\ 
( 
\'WI! 
( 
\lllm 
( 
\'WI! 
( 
\'WI! 
( 
( 
Yts'No ( 
Yes.· ( 
) 
) 
) 
) 0 
) 0 
) 0 
) 0 
) 
) 0 
) 0 
) 
) 
) 0 
) 0 
) 0 
) 
) 0 
) 
) 
) 


GS-9876/Filgotinib
Protocol GS-US-437-4093
Final
Gilead Sciences, Inc. 
Amendment 2
CONFIDENTIAL
Page 113
21 March 2018
Appendix 9.
Physician’s Global Assessment of Disease Activity
A horizontal visual analog scale will be used to record the physician’s assessment of the patient’s 
LMN disease activity.
Instructions: 
Place a mark on the line below to indicate the subject’s current LMN disease activity 
(independent of the subject’s self-assessment):
No LMN disease activity                                                                                 Maximum LMN disease activity


GS-9876/Filgotinib
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Final
Gilead Sciences, Inc. 
Amendment 2
CONFIDENTIAL
Page 114
21 March 2018
Appendix 10.
Patient Global Assessment of Disease Activity
A horizontal, visual analog scale will be used to provide the subject’s overall assessment of 
LMN disease activity.
Instructions:
Place a mark on the line below to indicate how active your lupus has been over the 
last week:
I have no lupus
                                
I have the worst lupus


GS-9876/Filgotinib
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Final
Gilead Sciences, Inc. 
Amendment 2
CONFIDENTIAL
Page 115
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Appendix 11.
36-Item Short Form Health Survey


 
SF-36v2® Health Survey © 1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)) 
 
 
Your Health and Well-Being 
 
 
This survey asks for your views about your health.  This information will help 
keep track of how you feel and how well you are able to do your usual activities. 
Thank you for completing this survey! 
 
For each of the following questions, please mark an 
 in the one box that best 
describes your answer. 
 
1. In general, would you say your health is: 
Excellent 
Very good 
Good 
Fair 
Poor 
 




  
 1 
  
 2 
  
 3 
  
 4 
  
 5 
 
 
 
2. Compared to one year ago, how would you rate your health in general 
now? 
Much better 
now than one 
year ago 
Somewhat 
better  
now than one 
year ago 
About the 
same as  
one year ago 
Somewhat 
worse  
now than one 
year ago 
Much worse 
now than one 
year ago 
 



 
  
 1 
  
 2 
  
 3 
  
 4 
  
 5 
 


 
SF-36v2® Health Survey © 1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)) 
3. The following questions are about activities you might do during a typical 
day.  Does your health now limit you in these activities?  If so, how much?  
 
 
 
Yes,  
limited  
a lot 
Yes, 
limited  
a little 
No, not 
limited  
at all 
 



 
a Vigorous activities, such as running, lifting  
heavy objects, participating in strenuous sports ...................... 
 1 ............. 
 2 ............. 
 3 
 
b Moderate activities, such as moving a table, pushing  
a vacuum cleaner, bowling, or playing golf ............................ 
1 ............. 
 2 ............. 
3
 
c Lifting or carrying groceries .................................................... 
 1 ............. 
 2 ............. 
 3 
 
d Climbing several flights of stairs ............................................. 
 1 ............. 
 2 ............. 
 3 
 
e Climbing one flight of stairs .................................................... 
 1 ............. 
 2 ............. 
 3 
 
f Bending, kneeling, or stooping ................................................ 
 1 ............. 
 2 ............. 
 3 
 
g Walking more than a mile ........................................................ 
 1 ............. 
 2 ............. 
 3 
 
h Walking several hundred yards ............................................... 
 1 ............. 
 2 ............. 
 3 
 
i Walking one hundred yards ..................................................... 
 1 ............. 
 2 ............. 
 3 
 
j Bathing or dressing yourself .................................................... 
 1 ............. 
 2 ............. 
 3 


 
SF-36v2® Health Survey © 1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)) 
4. During the past 4 weeks, how much of the time have you had any of the 
following problems with your work or other regular daily activities as a 
result of your physical health? 
 
All of  
the time 
Most of 
the time 
Some of  
the time 
A little of 
the time 
None of 
the time 
 



 
 
a Cut down on the amount of  
time you spent on work or  
other activities ................................. 
 1 .............. 
 2 .............. 
 3 .............. 
 4 ............. 
 5 
 
b Accomplished less than you  
would like ........................................ 
 1 .............. 
 2 .............. 
 3 .............. 
 4 ............. 
 5 
 
c Were limited in the kind of  
work or other activities .................... 
 1 .............. 
 2 .............. 
 3 .............. 
 4 ............. 
 5 
 
d Had difficulty performing the  
work or other activities (for  
example, it took extra effort) ........... 
 1 .............. 
 2 .............. 
 3 .............. 
 4 ............. 
 5 
 
 
5. During the past 4 weeks, how much of the time have you had any of the 
following problems with your work or other regular daily activities as a 
result of any emotional problems (such as feeling depressed or anxious)? 
 
All of  
the time 
Most of 
the time 
Some of  
the time 
A little of 
the time 
None of 
the time 
 



 
 
a Cut down on the amount of  
time you spent on work or  
other activities ................................. 
 1 .............. 
 2 .............. 
 3 .............. 
 4 ............. 
 5 
 
b Accomplished less than you  
would like ........................................ 
 1 .............. 
 2 .............. 
 3 .............. 
 4 ............. 
 5 
 
c Did work or other activities  
less carefully than usual ................... 
 1 .............. 
 2 .............. 
 3 .............. 
 4 ............. 
 5 


 
SF-36v2® Health Survey © 1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)) 
6. During the past 4 weeks, to what extent has your physical health or 
emotional problems interfered with your normal social activities with 
family, friends, neighbors, or groups? 
Not at all 
Slightly 
Moderately 
Quite a bit 
Extremely 
 



 
  
 1 
  
 2
 
3
 
4
  
 5 
 
 
 
 
 
7. How much bodily pain have you had during the past 4 weeks? 
None 
Very mild 
Mild 
Moderate 
Severe 
Very severe 
 




  
 1 
  
 2 
 
3
 
4
 
5
  
 6 
 
 
 
 
 
8. During the past 4 weeks, how much did pain interfere with your normal 
work (including both work outside the home and housework)? 
Not at all 
A little bit 
Moderately 
Quite a bit 
Extremely 
 



 
  
 1 
  
 2
 
3
 
4
  
 5 


 
SF-36v2® Health Survey © 1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)) 
9. These questions are about how you feel and how things have been with you 
during the past 4 weeks.  For each question, please give the one answer that 
comes closest to the way you have been feeling.  How much of the time 
during the past 4 weeks… 
 
 
10. During the past 4 weeks, how much of the time has your physical health or 
emotional problems interfered with your social activities (like visiting with 
friends, relatives, etc.)? 
All of  
the time 
Most of  
the time 
Some of  
the time 
A little of  
the time 
None of  
the time 
 



 
  
 1 
  
 2 
 
3
 
4
  
 5 
 
All of  
the time 
Most of  
the time 
Some of 
the time 
A little of the 
time 
None of 
the time 
 





 
a Did you feel full of life? ..................
 1 ..............
 2 ..............
 3 ..............
 4 ..............
 5 
 
b Have you been very nervous? ..........
 1 .............. 
 2 ..............
 3 ..............
 4 ..............
 5 
 
c Have you felt so down in the  
dumps that nothing could  
cheer you up? ...................................
 1 ..............
 2 ..............
 3 ..............
 4 ..............
 5
 
d Have you felt calm and   
peaceful? ..........................................
 1 .............. 
 2 ..............
 3 ..............
 4 ..............
 5
 
e Did you have a lot of energy? ..........
 1 ..............
 2 ..............
 3 ..............
 4 ..............
 5 
 
f Have you felt downhearted  
and depressed? .................................
 1 .............. 
 2 ..............
 3 ..............
 4 ..............
 5
 
g Did you feel worn out? ....................
 1 .............. 
 2 ..............
 3 ..............
 4 ..............
 5 
 
h Have you been happy? .....................
 1 .............. 
 2 ..............
 3 ..............
 4 ..............
 5 
 
i Did you feel tired? ...........................
 1 ..............
 2 ..............
 3 ..............
 4 ..............
 5 


 
SF-36v2® Health Survey © 1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)) 
11. How TRUE or FALSE is each of the following statements for you? 
 
Definitely 
true 
Mostly  
true 
Don’t  
know 
Mostly  
false 
Definitely 
false 

 


 
a I seem to get sick a little 
easier than other people .................. 
 1 .............. 
 2 ............. 
 3 .............. 
 4 .............. 
 5
 
b I am as healthy as  
anybody I know .............................. 
 1 .............. 
 2 ............. 
 3 .............. 
 4 .............. 
 5
 
c I expect my health to  
get worse ......................................... 
 1 .............. 
 2 ............. 
 3 .............. 
 4 .............. 
 5 
 
d My health is excellent ..................... 
 1 .............. 
 2 ............. 
 3 .............. 
 4 .............. 
 5
 
 
 
 
 
 
 
Thank you for completing these questions! 

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 2, Randomized, Double-Blind, Multicenter Study 
Evaluating the Safety and Efficacy of Filgotinib and 
GS-9876 in Subjects with Lupus Membranous Nephropathy 
(LMN)
Name of Test Drug:
Filgotinib and Lanraplenib (GS-9876)
Study Number:
GS-US-437-4093
Protocol Version (Date):
Amendment 2 (21 March 2018)
Analysis Type:
Final Analysis
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
28 January 2020
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(r) GILEAU 


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TABLE OF CONTENTS
STATISTICAL ANALYSIS PLAN..............................................................................................................................1
TABLE OF CONTENTS ..............................................................................................................................................1
LIST OF IN-TEXT TABLES........................................................................................................................................2
LIST OF IN-TEXT FIGURES ......................................................................................................................................2
LIST OF ABBREVIATIONS........................................................................................................................................3
1.
INTRODUCTION ................................................................................................................................................4
1.1.
Study Objectives ......................................................................................................................................4
1.2.
Study Design............................................................................................................................................4
1.3.
Sample Size and Power............................................................................................................................6
2.
TYPE OF PLANNED ANALYSIS ......................................................................................................................7
2.1.
Interim Analyses ......................................................................................................................................7
2.2.
Final Analysis ..........................................................................................................................................7
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES..............................................................................8
3.1.
Analysis Sets............................................................................................................................................8
3.1.1.
All Randomized Analysis Set.................................................................................................8
3.1.2.
Full Analysis Set ....................................................................................................................8
3.1.3.
Safety Analysis Set.................................................................................................................8
3.2.
Subject Grouping .....................................................................................................................................8
3.3.
Strata and Covariates................................................................................................................................9
3.4.
Examination of Subject Subgroups..........................................................................................................9
3.5.
Multiple Comparisons..............................................................................................................................9
3.6.
Missing Data and Outliers........................................................................................................................9
3.6.1.
Missing Data ..........................................................................................................................9
3.6.2.
Outliers...................................................................................................................................9
3.7.
Data Handling Conventions and Transformations ...................................................................................9
3.8.
Analysis Visit Windows.........................................................................................................................10
3.8.1.
Definition of Study Day .......................................................................................................10
3.8.2.
Analysis Visit Windows.......................................................................................................11
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window................................................................................................................................12
4.
SUBJECT DISPOSITION ..................................................................................................................................14
4.1.
Subject Enrollment and Disposition.......................................................................................................14
4.2.
Extent of Study Drug Exposure and Adherence.....................................................................................15
4.2.1.
Duration of Exposure to Study Drug....................................................................................15
4.2.2.
Adherence to Study Drug.....................................................................................................15
4.3.
Protocol Deviations................................................................................................................................15
5.
BASELINE CHARACTERISTICS....................................................................................................................16
5.1.
Demographics ........................................................................................................................................16
5.2.
Other Baseline Characteristics ...............................................................................................................16
5.3.
Medical History......................................................................................................................................17
6.
EFFICACY ANALYSES ...................................................................................................................................18
6.1.
Primary Efficacy Endpoint.....................................................................................................................18
6.1.1.
Statistical Hypothesis for the Primary Efficacy Endpoint....................................................18


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6.1.2.
Analysis of the Primary Efficacy Endpoint..........................................................................18
6.2.
Secondary Efficacy Endpoints ...............................................................................................................18
6.2.1.
Definitions of Key Secondary Efficacy Endpoints...............................................................18
6.2.2.
Analysis Methods for Secondary Efficacy Endpoints..........................................................18
6.3.
Exploratory Efficacy Endpoints.............................................................................................................19
6.3.1.
Definition of Exploratory Efficacy Endpoints......................................................................19
6.3.2.
Analysis Methods for Exploratory Efficacy Endpoints........................................................20
7.
SAFETY ANALYSES........................................................................................................................................21
7.1.
Adverse Events and Deaths....................................................................................................................21
7.1.1.
Adverse Event Dictionary ....................................................................................................21
7.1.2.
Adverse Event Severity........................................................................................................21
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................21
7.1.4.
Serious Adverse Events........................................................................................................21
7.1.5.
Treatment-Emergent Adverse Events...................................................................................21
7.1.5.1.
Definition of Treatment-Emergent Adverse Events .......................................21
7.1.5.2.
Incomplete Dates ............................................................................................22
7.1.6.
Summaries of Adverse Events and Deaths...........................................................................22
7.2.
Laboratory Evaluations ..........................................................................................................................24
7.2.1.
Summaries of Numeric Laboratory Results .........................................................................24
7.2.2.
Graded Laboratory Values ...................................................................................................24
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities.............................................25
7.2.2.2.
Summaries of Laboratory Abnormalities........................................................25
7.2.3.
Liver-related Laboratory Evaluations...................................................................................25
7.3.
Body Weight and Vital Signs.................................................................................................................25
7.4.
Prior and Concomitant Medications.......................................................................................................25
7.5.
Electrocardiogram Results .....................................................................................................................25
7.6.
Changes From Protocol-Specified Safety Analyses...............................................................................25
8.
SOFTWARE.......................................................................................................................................................26
9.
SAP REVISION..................................................................................................................................................27
10.
APPENDICES ....................................................................................................................................................28
Appendix 1.
Schedule of Assessments........................................................................................................28
LIST OF IN-TEXT TABLES
Table 1-1.
Study Treatments......................................................................................................................5
Table 3-1.
Target Days for Analysis Visits..............................................................................................11
LIST OF IN-TEXT FIGURES
Figure 1-1.
Study Design Schematic...........................................................................................................5


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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BLQ
below the limit of quantitation
BMI
body mass index
CI
confidence interval
CRF
case report form
CSR
clinical study report
CTCAE
Common Toxicity Criteria for Adverse Events
DMC
data monitoring committee
ECG
Electrocardiogram
eGFR
estimated glomerular filtration rate
ET
early termination
FAS
Full Analysis Set
HLT
high-level term
ICH
International Conference on Harmonization (of Technical Requirements for Registration of 
Pharmaceuticals for Human Use)
IWRS
interactive web response system
LLN
low limit of normal
LLT
lower-level term
LMN
Lupus Membranous Nephropathy
LOQ
limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
PT
preferred term
PTM
placebo to match
Q1, Q3
first quartile, third quartile
SAP
statistical analysis plan
SD
standard deviation
SOC
system organ class
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
upper limit of normal
UPCR
urine protein creatinine ratio
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study report (CSR) 
for Study GS-US-437-4093. This SAP is based on the study protocol amendment 2 dated 
21 March 2018 and the electronic case report forms (eCRF). The SAP will be finalized before 
database finalization. Any changes made after the finalization of the SAP will be documented in 
the CSR.
The decision to discontinue the study due to enrollment challenges has been made on
18 December 2018. The screening has been stopped on 01 February 2019, with total 9 subjects 
enrolled in the study. Enrolled subjects were allowed to complete participation in the study up to 
Week 52.
This SAP describes the analyses to support the abbreviated CSR. 
1.1.
Study Objectives
The primary objective of this study is as follows:

To evaluate the efficacy of filgotinib and lanraplenib in subjects with LMN
The secondary objectives of this study are as follows:

To evaluate the safety and tolerability of filgotinib and lanraplenib in subjects with LMN

To evaluate the PK of filgotinib and lanraplenib in subjects with LMN
The exploratory objectives are:
 
 
1.2.
Study Design
This is a Phase 2, randomized, double-blind, multicenter study to evaluate the safety and efficacy 
of filgotinib and lanraplenib in subjects with active LMN who are not in partial or complete 
remission in response to treatment with one or more anti-inflammatory or immunosuppressive 
agents.
A schematic of this study is provided in Figure 1-1.
CCII 
I 


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Figure 1-1.
Study Design Schematic
Eligible subjects were randomized in a blinded fashion to 1 of 2 treatment arms in 1:1 ratio using 
a computerized IWRS system to receive once daily oral dose of the following study drugs 
starting on Day 1 for 16 weeks:
Table 1-1.
Study Treatments
Treatment Arm
Study Drugs
Filgotinib (n=16) 
filgotinib 200 mg + PTM lanraplenib 30 mg
Lanraplenib (n=16) 
lanraplenib 30 mg + PTM filgotinib 200 mg
PTM = placebo to match
Randomization will be stratified by prior treatment with cyclophosphamide.
Urinary protein excretion was determined using 2 methods two consecutive morning voids as 
well as a 24-hour urine collection. For the Day 1 assessment, all 3 urine samples will be 
collected prior to Day 1, with the 24-hour urine collection as close to the Day 1 visit as possible. 
RANDOMIZATION 
1:1 
(N=32) 
DAYl 
Baseline 
Blinded Treatment Phase 
WK16 
1° Endpoint 
GS-9876 30 me + 
PTM Filgotinib 
W 16: Subjecuwlth a? 35"reductionln 
urinary proteinexaetion tromBas.eline(Dav 1) 
t.o Wee.. 16wil ccntinue to receive their 
anicn~ blind~ stuO{ ttentnl!nt for Bn 
additional 16weeks. 
Subjectsthatdo notachN!'l4! a~ 3SS6 redtetian 
in urinary protii!!il ex:ration wil switch study 
tr•aunent. 
WK32 
Extended Blinded 
Treatment Phase 
Filgotinib200 mg+ 
PTM GS-9876 
GS-9876 30 mg + 
PTM Filgotinib 
GS-9876 30 mg + 
PTM Filgotinib 
Filgotinib200 mg+ 
PTM GS-9876 
WK 32: Subjec,:;with a? 35" reduction in urinary 
protl!in l!!lCl'l!lian from Oayl {for slJJj~who 
remained on the ranckrnized st'lJdy treatmenta·tta-
Wee 16)orfromWee 16{forsub~tswho 
switched rreatme,uatWeek 16lwilcontinueto 
receive their a~gnedblinded study t~attnentfor 
an additional 20weelu. 
SubjKtsthartdo no11dl•w a? 35iireduction in 
urin•ry protein 
from O.y 1 (for .5UbjKt:s 
who remained on thl randomized stua,, UHtmant 
aftuWHlc 16jorfrom WHk 16(for slJbjeruwho 
switched trntmeit at Week 16ltoWeek 32 con 
continuewhichwer treatment led to the creat:u 
reduction in urinilry protein uaet.ian (from OiiY 1 
roWee lc 16on initial study~atmenrorfrom 
W ee 16 to Week 32 onswftd"ted treatmen , or 
eithu stuOf treiiltmi!nt per che lnvestgiilCDr"5 
discretia,. 
WK52 WK56 
Follow-Up 


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At Week 16, the primary study endpoint will be assessed by urine protein excretion during a 
24-hour urine collection. Two consecutive morning voids prior to the Week 16 visit will be used 
to determine response for subsequent study treatment. All subjects who achieve a ≥ 35% 
reduction in urinary protein excretion (using an average of the urine protein creatinine ratio 
(UPCR) from 2 morning voids) from Day 1 will continue to receive their assigned blinded study 
treatment (filgotinib 200 mg + PTM lanraplenib, or lanraplenib 30 mg + PTM filgotinib) for an 
additional 16 weeks. Additional details regarding urine collection procedures will be specified in 
the Laboratory Manual and Subject Procedures Manual.
Subjects who do not achieve a ≥ 35% reduction in urinary protein excretion from Day 1 to 
Week 16 will switch study treatment in a blinded fashion (ie, those on filgotinib will switch to 
lanraplenib + PTM filgotinib, while those on lanraplenib will switch to filgotinib + PTM 
lanraplenib).
After 32 weeks of blinded treatment, those who have a ≥ 35% reduction in urinary protein
excretion (using an average of the UPCR from 2 morning voids) from Day 1 (for subjects who 
remained on the randomized study treatment after Week 16) or from Week 16 (for subjects who 
switched treatment at Week 16) will continue their assigned blinded treatment for an additional 
20 weeks in the Extended Blinded Treatment Phase. Subjects that do not achieve a ≥ 35% 
reduction in urinary protein excretion from Day 1 (for subjects who remained on the randomized 
study treatment after Week 16) or from Week 16 (for subjects who switched treatment at 
Week 16) to Week 32 will be allowed to continue whichever treatment led to the greatest 
reduction in urinary protein excretion (from Day 1 to Week 16 on initial study treatment or from 
Week 16 to Week 32 on switched treatment), or either study treatment per the Investigator’s 
discretion (eg, differences in tolerability or other non-renal benefits that support overriding the 
treatment assignment according to reduction in urinary protein excretion) during the Extended 
Blinded Treatment Phase.
1.3.
Sample Size and Power
The sample size was chosen based on the practical considerations and to ensure that a clinically 
meaningful reduction in proteinuria from Baseline (Day 1) could be detected in any of the 
treatment groups, filgotinib or lanraplenib. With 16 subjects per treatment group (32 subjects 
total), there is a 80% power to detect a 35% reduction from Baseline (Day 1) in proteinuria at 
Week 16 with a standard deviation of 50% and a 2-sided 0.05 significance level. 
The enrollment was stopped after 9 subjects were randomized. 


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
The first DMC data review meeting was planned to be conducted after approximately 50% of 
planned subjects enrolled and completed through 16 weeks of study treatment. 
Due to early closure of the study enrollment, required number of subjects for the first planned 
DMC review was not reached. Therefore, no data reviews were performed by DMC. 
2.2.
Final Analysis
After all subjects have completed the study, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned 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 provided; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD), median, first quartile (Q1), 
third quartile (Q3), minimum, and maximum will be presented.
By-subject listings will be presented for all subjects in the All Randomized Analysis Set and 
sorted by subject ID number, visit date, and time (if applicable). Data collected on log forms, 
such as AEs, will be presented in chronological order within the subject. The treatment group to 
which subjects were randomized will be provided 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 and the reasons for their exclusion, will 
be summarized by treatment group.
A listing of reasons for exclusion from analysis sets will be provided by subject.
3.1.1.
All Randomized Analysis Set
All Randomized Analysis Set includes all subjects who were randomized in the study. This is the 
primary analysis set for by-subject listings.
3.1.2.
Full Analysis Set
The Full Analysis Set (FAS) includes all randomized subjects who took at least 1 dose of study 
drug (filgotinib, lanraplenib). This is the primary analysis set for efficacy analyses.
3.1.3.
Safety Analysis Set
The Safety Analysis Set includes all subjects who took at least 1 dose of study drug. This is the 
primary analysis set for safety analyses. All data collected during treatment plus 30 days after the 
last dose of any study drug will be included in the safety summaries.
3.2.
Subject Grouping
For analyses based on the FAS, subjects will be grouped according to the treatment to which 
they were initially randomized at Study Day 1. For analyses based on the Safety Analysis Set, 


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subjects will be grouped according to the actual treatment 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.
3.3.
Strata and Covariates
Subjects were randomly assigned to treatment groups via the interactive voice or web response 
system (IXRS) in a 1:1 ratio using a stratified randomization schedule. Stratification was based 
on the prior treatment with cyclophosphamide.
The stratification factor values recorded in IXRS will be used for analyses.
3.4.
Examination of Subject Subgroups
There are no prespecified subject subgroups for efficacy and safety analyses.
3.5.
Multiple Comparisons
Adjustments for multiplicity will not be applied. 
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.
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
The following conventions will be used for the imputation of date of birth when it is partially 
missing or not collected:

If only month and year of birth is collected, then “01” will be imputed as the day of birth

If only year of birth is collected, then “01 July” will be imputed as the day and month of birth

If year of birth is missing, then date of birth will not be imputed


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In general, age (in years) collected at Day 1 will be used for analyses and presented in listings. If 
age at Day 1 is not available for a subject, then age derived based on date of birth and the Day 1 
visit date will be used instead. If an enrolled subject was not dosed with any study drug, the 
randomization date will be used instead of the Day 1 visit date. For screen failures, the date the 
first informed consent was signed will be used for the age derivation. 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.
The 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).
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 postdose 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 first dose of study drug administration.
The study day for treatment period 2 (From Week 16 to Week 32) / period 3 (from Week 32 to 
study end) will be calculated as: Assessment Date Date of the first dose of the corresponding
treatment period (Day 1 for treatment period 1; Week 16 for treatment period 2 and Week 32 for 
treatment period 3) + 1. The dates of the first dose of the study drug dispensed at 
Day 1/Week 16/Week 32 are recorded on CRF. 


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3.8.2.
Analysis Visit Windows
The target study days for analysis visits are provided in the Table 3-1
Table 3-1.
Target Days for Analysis Visits
The nominal visit as recorded on the CRF will be used when data are summarized by visit. Any 
data relating to unscheduled visits will not be assigned to a particular visit or time point. 
However, the following exceptions will be made:
Nominal Visit
Study Day from Day 1/
From Week 16/From Week 32 
Screening 
<1
Baseline
<=1
Week 1
8
Week 2 
15
Week 4 
29
Week 8
57
Week 12
85
Week 16
113/1
Week 18
127/15
Week 20
141/29
Week 24 
169/57
Week 28
197/85
Week 32
225/113/1
Week 36
253/141/29
Week 40
281/169/57
Week 44
309/197/85
Week 48
337/225/113
Week 52
365/253/141
Follow-up Visit
NA


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
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.

The early termination (ET) data will be presented as a separate visit and labeled “ET Visit”.

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.
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value.
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 nominal 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:


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
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 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 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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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by treatment group 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.
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 treatment period with the following
categories:

Completed study up to Week 16, Week 32, and through the end of the study

Completed study drug up to Week 16, Week 32, and through the end of study

Did not complete the study/study drug up to Week 16, Week 32, and through the end of 
study with reasons for premature discontinuation of the study/study drug

Treatment switched at Week 16/Week 32
For the status of study drug and study completion, and reasons for discontinuation, the number 
and percentage of subjects in each category will be provided. The denominator for the 
percentage calculation will be the total number of subjects in the Safety Analysis Set 
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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 relative 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 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 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.
The total duration of exposure to study drug will be summarized using descriptive statistics and 
categorical summary (number and percentage of subjects exposed). Summaries will be provided 
by treatment group for the Safety Analysis Set. No formal statistical testing is planned.
4.2.2.
Adherence to Study Drug
An adherence to study drug will not be summarized.
A by-subject listing of study drug administration will be provided by subject ID number (in 
ascending order) and visit (in chronological order).
4.3.
Protocol Deviations 
A by-subject listing will be provided for those subjects who did not meet at least 1 eligibility 
(inclusion or exclusion) criterion. The listing will present the eligibility criterion (or criteria if 
more than 1 deviation) that subjects did not meet and related comments, if collected.
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. A by-subject listing will be provided for the subjects with important protocol 
deviation.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics
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. 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)

Sex
A by-subject demographic listing, including the informed consent date, will be provided by
subject ID number in ascending order.
5.2.
Other Baseline Characteristics
The baseline characteristics include:

Prior treatment with cyclophosphamide (Yes, No)

24-hour urine protein (< 3g/d, >  3g/d)

Baseline 24-hour urine protein

Baseline eGFR

Baseline UPCR (average of 2 morning voids)

UPCR from a 24-hour urine collection

Current treatment with systemic corticosteroids (Yes, No)
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.


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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 listed.


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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoint
The primary endpoint is the percent change in urine protein from Baseline (Day 1) to Week 16. 
Urine protein is assessed by urinary protein excretion during a 24-hour urine collection.
6.1.1.
Statistical Hypothesis for the Primary Efficacy Endpoint
No statistical hypotheses will be tested.
6.1.2.
Analysis of the Primary Efficacy Endpoint
The primary endpoint, the percent change from Baseline (Day 1) in 24-hour proteinuria at
Week 16 will be presented in descriptive statistics for each treatment group.
6.2.
Secondary Efficacy Endpoints
6.2.1.
Definitions of Key Secondary Efficacy Endpoints
The secondary efficacy endpoints include:

Change from Baseline (Day 1) in urine protein (assessed by urine protein excretion during a 
24-hour urine collection) at Week 16

Change from Baseline (Day 1) in eGFR at Week 16

Change from Baseline (Day 1) in UPCR (assessed by urine protein excretion during a
24-hour urine collection) at Week 16

Proportion of subjects with partial remission (defined as urine protein excretion below 
< 3 g/d and urine protein excretion decrease by ≥ 50% among subjects with Baseline (Day 1) 
nephrotic range proteinuria [urine protein excretion ≥ 3 g/d]; or urine protein excretion 
decrease by ≥ 50% among subjects with subnephrotic range proteinuria [urine protein 
excretion < 3 g/d]) at Week 16

Proportion of subjects with complete remission (defined as urine protein excretion below 
0.5 g/day, with no hematuria) at Week 16
6.2.2.
Analysis Methods for Secondary Efficacy Endpoints
The absolute changes and relative changes from baseline by visit will be provided in the 
descriptive summaries. Secondary endpoints and their components will be presented in listings. 


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6.3.
Exploratory Efficacy Endpoints
6.3.1.
Definition of Exploratory Efficacy Endpoints
The exploratory efficacy endpoints include:
 
 
 
 
 
 
 
 
CCI
CCI
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 


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6.3.2.
Analysis Methods for Exploratory Efficacy Endpoints
 
CCI


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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the 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 safety database from the Pharmacovigilance & 
Epidemiology Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

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.
TEAEs of treatment period Up to Week 16 are defined as 1 or both of the following:


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
Any AEs with an onset date on or after first dosing date of a treatment period, prior to the 
first dose of treatment at Week16. For subjects who did not continue treatment past Week 16, 
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 Week 16 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.
A brief, high-level summary of the number and percentage of subjects who experienced at least 
1 TEAE in the categories described below will be provided by treatment group. All deaths
observed in the study will also be included in this summary.
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, PT, severity and treatment group for the following:

All TEAEs

All TE treatment-related AEs

All TE SAEs

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For the AE categories described below, summaries will be provided by SOC, PT, and treatment 
group:

TEAEs of Grade 3 or higher (by maximum severity)

TE treatment-related AEs of Grade 3 or higher (by maximum severity)

All TE treatment-related SAEs

All TEAEs leading to premature discontinuation of study drug

All TEAEs leading to premature discontinuation of study
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 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, data listings will be provided for the following:

All AEs, indicating whether the event is treatment emergent

SAEs

Deaths

AEs leading to premature discontinuation of study drug or study

TEAEs of interest
Adverse events of interest will be identified by the use of either Standardized MedDRA queries 
or MedDRA search terms. 
The following adverse events of interest will be presented:

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)

Herpes Zoster infection

Opportunistic infections

Active tuberculosis

Hepatitis B and C


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
Serious Major Adverse Cardiovascular Events (MACE)
Unstable angina
Cardiac failure
Stroke
Transient ischemic attack
Percutaneous coronary intervention 
Myocardial Infarction

Gastrointestinal perforation

Venous thrombotic events and pulmonary embolism

Malignancy including non-melanoma skin cancer

Transaminases increased
7.2.
Laboratory Evaluations
The TE laboratory abnormalities will be reported by the treatment period.
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 for laboratory tests will not be provided. Hematology, chemistry and 
urinalysis results will be listed. 
7.2.2.
Graded Laboratory Values
The CTCAE v4.03 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. 


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7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of study drug plus 30 days for subjects who permanently discontinued study drug. If the 
relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed 
within the time frame specified above will be considered treatment emergent.
The listing of all laboratory abnormalities will be provided.
7.2.2.2.
Summaries of Laboratory Abnormalities
The summaries (number and percentage of subjects) of treatment-emergent laboratory 
abnormalities will be provided by lab test; subjects will be categorized according to the most 
severe postbaseline abnormality grade for a given lab test.
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
nonmissing postbaseline values within study period.
A by-subject listing of treatment-emergent Grade 3 or 4 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 laboratory evaluations will be presented as part of chemistry results. 
7.3.
Body Weight and Vital Signs
Body weight and vital signs will be listed.
7.4.
Prior and Concomitant Medications
Prior and concomitant medications will be listed. 
7.5.
Electrocardiogram Results
Electrocardiogram results (overall assessment and 12-lead ECG) data will be listed. 
7.6.
Changes From Protocol-Specified Safety Analyses
Only limited safety summaries are provided due to low number of subjects enrolled in the study 
prior to study termination.


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8.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.


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9.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


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10.
APPENDICES
Appendix 1.
Schedule of Assessments
Appendix 1.
Schedule of Assessments
Visit Window (Days)
Blinded Treatment Phase
Extended Blinded 
Treatment Phase
End of 
Study
Unscheduled 
Visit 
(exacerbation 
of LMN)f
Screena
D1/
Baseline
Week 1
Weeks 2, 4, 8, 
12, 18, 20, 24, 
28
Week 16b
Week 32c
Weeks 36,
40, 44, 48
Week 52
F/Ud
ETe
-35
0
±3
±3
±3
±3
±5
±5
±5
±5
Written Informed 
Consent
X
Medical History, 
including kidney 
biopsy report
X
Review 
Inclusion/Exclusion 
Criteria
X
X
Randomization
X
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
Complete Physical 
Examination
X
X
X
Symptom driven 
Physical Examinationg
X
X
X
X
X
X
X
X
2 Morning voids & 
24 hour Urine 
Collectionh
Xh
Xh
Xh
Xh
Xh
Xh
Urinalysisi
X
X
X
X
X
X
X
X
X


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Visit Window (Days)
Blinded Treatment Phase
Extended Blinded 
Treatment Phase
End of 
Study
Unscheduled 
Visit 
(exacerbation 
of LMN)f
Screena
D1/
Baseline
Week 1
Weeks 2, 4, 8, 
12, 18, 20, 24, 
28
Week 16b
Week 32c
Weeks 36,
40, 44, 48
Week 52
F/Ud
ETe
-35
0
±3
±3
±3
±3
±5
±5
±5
±5
SELENA SLEDAI j, bb
X
X
X
X
X
X
X
BILAG k, bb
X
X
X
X
X
Patient Global 
Assessment of disease 
activityl, bb
X
X
X
X
X
Physician Global 
Assessment of disease 
activitym, bb
X
X
X
X
X
36 Item Short Form 
Health Survey bb
X
X
X
X
X
Vital Signsn
X
X
X
X
X
X
X
X
X
X
X
ECG
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
Serum Chemistry
X
X
X
X
X
X
X
X
X
X
Fasting Lipids
X
X
X
X
Coagulation
X
X
X
X
X
X
X
X
X
X
HbA1c and TSH
X
CRP and ESR
X
X
X
X
X
X
X
X
X
X
Quantitative Serum 
Immunoglobulin Test
X
Xcc
Xdd
Autoantibody Panel & 
Complement Levels
X
X
Xz
X
X
X
X
X
Serum Pregnancy Testo
X
Urine Pregnancy Testo, p
X
X
X
X
X
X
X
X
X
X
FSH Testq
X


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Visit Window (Days)
Blinded Treatment Phase
Extended Blinded 
Treatment Phase
End of 
Study
Unscheduled 
Visit 
(exacerbation 
of LMN)f
Screena
D1/
Baseline
Week 1
Weeks 2, 4, 8, 
12, 18, 20, 24, 
28
Week 16b
Week 32c
Weeks 36,
40, 44, 48
Week 52
F/Ud
ETe
-35
0
±3
±3
±3
±3
±5
±5
±5
±5
HIV 1/2, HBV, HCV 
Serology
X
HCV RNA VLr
X
X
X
X
X
X
X
X
X
X
QuantiFERON®
TB Gold in Tube Tests
X
Chest X Rays
X
Plasma PK Samplet
X
X
X
Urine PK Samplesu
X
Whole Blood TBNK 
Biomarker Sample
X
X
Xx
X
X
X
X
X
Serum Biomarker 
Sample
X
X
Xx
X
X
X
X
X
Plasma Biomarker 
Sample
X
X
Xx
X
X
X
X
X
vfPBMC Sample
X
X
Xx
X
X
X
X
X
PAXgene RNA Sample
X
X
Xx
X
X
X
X
X
Urine Biomarker 
Sample
X
X
Xx
X
X
X
X
X
In Clinic Study Drug 
Administrationy
X
X
X
X
CCI


Lanraplenib (GS-9876)
GS-US-437-4093
Version 1.0
Statistical Analysis Plan – Final Analysis
Final
CONFIDENTIAL
Page 31
28 January 2020
Visit Window (Days)
Blinded Treatment Phase
Extended Blinded 
Treatment Phase
End of 
Study
Unscheduled 
Visit 
(exacerbation 
of LMN)f
Screena
D1/
Baseline
Week 1
Weeks 2, 4, 8, 
12, 18, 20, 24, 
28
Week 16b
Week 32c
Weeks 36,
40, 44, 48
Week 52
F/Ud
ETe
-35
0
±3
±3
±3
±3
±5
±5
±5
±5
Study Drug 
Accountability
X
X
X
X
X
X
X
Study Drug Dispensing
X
Xaa
X
X
X
Review AEs & 
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
a
Prospective subjects should be screened no more than 35 days prior to the administration of the first dose of study treatment. The Screening visit will take two separate days to 
complete. In addition, Screening Day 2 cannot occur earlier than 3 days after Screening Day 1 due to the timing of the morning urine voids and the 24 hour urine collection. 
b
Urinary protein excretion will be determined using 2 methods 2 consecutive morning voids as well as a 24 hour urine collection. For the Baseline assessment, all 3 urine 
samples will be collected prior to Day 1, with the 24 hour urine collection as close to the Day 1 visit as possible. At Week 16, the primary study endpoint will be assessed by 
urine protein excretion during a 24 hour urine collection. Two consecutive morning voids prior to the Week 16 visit will be used to determine response for subsequent study 
treatment. All subjects who achieve a ≥ 35% reduction in urinary protein excretion (using an average of the UPCR from the morning voids) from Baseline (Day 1) will 
continue to receive their assigned blinded study treatment (filgotinib 200 mg + PTM lanraplenib, or lanraplenib 30 mg + PTM filgotinib) for an additional 16 weeks. Subjects 
who do not achieve a ≥ 35% reduction in urinary protein excretion from Baseline (Day 1) to Week 16 will switch study treatment for 16 weeks in a blinded fashion (ie, those 
on filgotinib will switch to lanraplenib + PTM filgotinib, while those on lanraplenib will switch to filgotinib + PTM lanraplenib)
c
After 32 weeks of blinded treatment, those who have a ≥ 35% reduction in urinary protein excretion (using an average of the UPCR from 2 morning voids) from Day 1 
(for subjects who remained on the randomized study treatment after Week 16) or from Week 16 (for subjects who switched treatment at Week 16) will continue their assigned 
blinded treatment for an additional 20 weeks in the Extended Blinded Treatment Phase.  Subjects that do not achieve a ≥ 35% reduction in urinary protein excretion from 
Day 1 (for subjects who remained on the randomized study treatment after Week 16) or from Week 16 (for subjects who switched treatment at Week 16) to Week 32 will be 
allowed to continue whichever treatment led to the greatest reduction in urinary protein excretion (from Day 1 to Week 16 on initial study treatment or from Week 16 to 
Week 32 on switched treatment), or either study treatment per the Investigator’s discretion during the Extended Blinded Treatment Phase.
d
The Follow up (FU) Visit as detailed in the End of Study section of the Study Procedures Table will be completed 4 weeks after the last dose of study treatment. For subjects 
that complete the entire study, the FU visit will be conducted at Week 56.
e
Subjects who discontinue from the study for any reason will complete the Early Termination (ET) Visit at the time of study discontinuation. 
f
Subjects seen at an unscheduled visit for disease exacerbation (worsening of proteinuria, and/or decrease in eGFR) will complete the Unscheduled Visit assessments.
g
Symptom driven physical examinations will be performed, as needed, based on reported signs and symptoms.
h
Urinary protein excretion will be determined using 2 consecutive morning voids as well as a 24 hour urine collection. 
For the Day 1 assessment, all 3 urine samples will be collected prior to Day 1, with the 24 hour urine collection as close to the Day 1 visit as possible. 
For Week 16, subjects will submit 2 consecutive morning urine void samples to the study center approximately 7 days prior to the Week 16 visit to test their change in 
urinary protein excretion.  Subjects will also submit a 24 hour urine collection that is collected immediately prior to the Week 16 visit, or as close to the Week 16 visit as 
possible. These results will inform their treatment assignment for the additional 16 weeks.


Lanraplenib (GS-9876)
GS-US-437-4093
Version 1.0
Statistical Analysis Plan – Final Analysis
Final
CONFIDENTIAL
Page 32
28 January 2020
For Week 32, subjects will submit 2 consecutive morning urine void samples to the study center approximately 7 days prior to the Week 32 visit to test their change in 
urinary protein excretion.  Subjects will also submit a 24 hour urine collection that is collected immediately prior to the Week 32 visit, or as close to the Week 32 visit as 
possible. These results will inform their treatment assignment for the additional 20 weeks in the Extended Blinded Treatment Phase.
i
The urinalysis will include urine microscopy and spot protein to creatinine ratio. As contamination by menstrual blood may interfere with the primary endpoint, whether or 
not the patient is menstruating will be recorded on the CRF; microscopic urine examination will evaluate for active urine sediment (any of:  > 5 WBC/hpf [pyuria], 
> 5 RBC/hpf [hematuria], or red cell casts in the absence of infection or other causes). In such circumstances, investigators may ask patients to return for another screening 
visit.
j
Safety of Estrogens in Lupus Erythematosus National Assessment trial based SLE Disease Activity Index (SELENA SLEDAI)
k
British Isles Lupus Activity Group (BILAG) 
l
Patient global assessment of disease activity 
m
Physician global assessment of disease activity 
n
Vital signs include resting blood pressure, respiratory rate, heart rate, and body temperature. 
o
Females of childbearing potential only.
p
If a urine pregnancy test is positive, study drug should be immediately interrupted, and the subject should return to the site for a serum pregnancy test to confirm result.
q
Females of nonchildbearing potential only.
r
Subjects with positive HCV Ab, but negative HCV RNA VL at Screening are eligible per investigator judgment, but require ongoing monitoring during the study.
s
Subjects previously treated for latent TB or active TB described in Inclusion # 17 do not need to have the QuantiFERON®  TB Gold In Tube test (or equivalent assay) 
obtained, but a chest radiograph must be obtained if not done so within 3 months prior to screening (with the report or films available for investigator review). All other 
subjects must have the QuantiFERON® TB Gold In Tube test (or equivalent assay) obtained at screening AND a chest radiograph (views as per local guidelines) taken at 
screening or within the 3 months prior to screening (with the report or films available for investigator review).
t
Blood samples will be collected for plasma PK analysis of filgotinib and its active metabolite GS 829845, and lanraplenib post dose at Weeks 2, 4 and 20 (at least 30 minutes 
and up to 3 hours after dosing), anytime at Weeks 8 and 24, and within 2 hours prior to dosing at Weeks 16 and 32.
u
Urine PK analyses will be collected for lanraplenib, filgotinib and its active metabolite, GS 829845, using the 24h urine collection at Week 16.
 
 
  
x
Biomarker assessments will be collected at Week 2 only.
y
At Weeks 2, 4, and 20, subjects will be instructed to take their study drug in clinic as the first study procedure prior to any others scheduled for that visit. At Day 1, and 
Weeks 16 and 32, subjects will be instructed to take their study drug after predose assessments have been completed (eg, 2 hours after PK sample collection at Weeks 16 
and 32).
z
Autoantibody panel and complement levels will be collected at Weeks 2, 4, and 8 only.
aa
Study drug will be not be dispensed at Weeks 2 and 18.
bb
Questionnaires will be administered where available.
cc
Quantitative serum immunoglobulin testing will be performed at Week 8 and 24 only.
dd
Quantitative serum immunoglobulin testing will be performed at Week 48 only.
CCII 
I