A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-0976 in Subjects With Nonalcoholic Steatohepatitis
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis (NASH)
Sponsor: Gilead Sciences

Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Sciences Medical 
Monitor 
Protocol Version/Date: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study 
Evaluating the Safety, Tolerability, and Efficacy of GS-0976 in 
Subjects with Nonalcoholic Steatohepatitis 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
124915 
Not Applicable 
Not Available 
Nonalcoholic steatohepatitis (NASH) 
GS-US-426-3989 
Name: 
Telephone: 
Fax: 
Email: 
Original: 
Amendment 1: 
IPIPD 
IPIPD 
IPIPD 
PPU 
20 June 2016 
15 December 2016 
CONFIDENTIALITY STATEMENT 
The info1mation contained in this document, paiiicularly unpublished data, is the prope1iy or 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 infonnation is only to be used by you in 
connection with authorized clinical studies of the investigational diug described in the protocol. 
You will not disclose any of the infonnation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessaiy to obtain infonned consent from those 
persons to whom the di11g may be adininistered. 

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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....................................................................12
1.
INTRODUCTION ..............................................................................................................................................16
1.1.
Background ............................................................................................................................................16
1.2.
GS-0976 .................................................................................................................................................17
1.2.1.
General Information .............................................................................................................17
1.2.2.
Nonclinical Pharmacology ...................................................................................................17
1.2.3.
Nonclinical Toxicology........................................................................................................17
1.2.4.
Nonclinical Pharmacokinetics..............................................................................................18
1.2.5.
Clinical Trials of GS-0976 ...................................................................................................19
1.3.
Rationale for the Current Study .............................................................................................................24
1.3.1.
Rationale for this Study........................................................................................................25
1.4.
Risk/Benefit Assessment for the Study..................................................................................................26
1.5.
Compliance ............................................................................................................................................27
2.
OBJECTIVES.....................................................................................................................................................28
3.
STUDY DESIGN................................................................................................................................................29
3.1.
Study Design..........................................................................................................................................29
3.2.
Treatment Plan and Regimen .................................................................................................................29
3.3.
Biomarker Testing..................................................................................................................................30
3.3.1.
Biomarker Samples to Address the Study Objectives ..........................................................30
3.3.2.
Biomarker Samples for Optional Future Research...............................................................30
3.3.3.
Biomarker Samples for Optional Genomic Research...........................................................30
4.
SUBJECT POPULATION..................................................................................................................................31
4.1.
Number of Subjects and Subject Selection ............................................................................................31
4.2.
Inclusion Criteria....................................................................................................................................31
4.3.
Exclusion Criteria...................................................................................................................................32
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................35
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................35
5.1.1.
Procedures for Breaking Treatment Codes...........................................................................35
5.2.
Description and Handling of Study Drugs .............................................................................................36
5.2.1.
Formulation..........................................................................................................................36
5.2.2.
Packaging and Labeling .......................................................................................................36
5.2.3.
Storage and Handling...........................................................................................................36
5.3.
Dosage and Administration of GS-0976/PTM GS-0976........................................................................36
5.4.
Prior and Concomitant Medications.......................................................................................................37
5.5.
Accountability for GS-0976/PTM GS-0976 ..........................................................................................38
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................38
6.
STUDY PROCEDURES ....................................................................................................................................39
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................39
6.2.
Pretreatment Assessments......................................................................................................................39

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6.2.1.
Screening Visit .....................................................................................................................39
6.3.
Baseline/Day 1 Randomization and Assessments..................................................................................41
6.4.
Treatment Assessments..........................................................................................................................43
6.4.1.
Week 1 Visit (±3 days).........................................................................................................43
6.4.2.
Week 4 Visit (±3 days).........................................................................................................44
6.4.3.
Week 8 Visit (±3 days).........................................................................................................44
6.4.4.
Week 12 Visit (±7 days).......................................................................................................45
6.4.5.
Unscheduled Visit ................................................................................................................46
6.4.6.
Follow-Up Visit (±5 days) ...................................................................................................47
6.5.
Assessments for Premature Discontinuation from Study.......................................................................48
6.6.
Criteria for Discontinuation of Study Treatment....................................................................................48
6.7.
.48
6.8.
Description of Assessments ...................................................................................................................49
6.8.1.
Clinical Laboratory Analytes ...............................................................................................49
6.8.2.
Physical Examination...........................................................................................................50
6.8.3.
Vital Signs............................................................................................................................50
6.8.4.
Medical History....................................................................................................................51
6.8.5.
Pharmacogenomic Testing ...................................................................................................51
6.8.6.
Health Related Quality of Life (HRQoL).............................................................................51
6.8.7.
Electrocardiogram................................................................................................................51
6.8.8.
FibroScan® ...........................................................................................................................51
6.8.9.
MRE and MRI-PDFF...........................................................................................................52
6.9.
End of Study Definition .........................................................................................................................52
6.10.
Poststudy Care........................................................................................................................................52
6.11.
Sample Storage.......................................................................................................................................52
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................53
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................53
7.1.1.
Adverse Events.....................................................................................................................53
7.1.2.
Serious Adverse Events........................................................................................................53
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................54
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................54
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................54
7.2.2.
Assessment of Severity ........................................................................................................55
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................55
7.4.
Gilead Reporting Requirements.............................................................................................................56
7.5.
Toxicity Management ............................................................................................................................57
7.6.
Special Situations Reports......................................................................................................................59
7.6.1.
Definitions of Special Situations..........................................................................................59
7.6.2.
Instructions for Reporting Special Situations.......................................................................60
8.
STATISTICAL CONSIDERATIONS................................................................................................................62
8.1.
Analysis Objectives and Endpoints........................................................................................................62
8.1.1.
Analysis Objectives..............................................................................................................62
8.1.2.
Primary Endpoint .................................................................................................................62
8.1.3.
Exploratory Efficacy Endpoints ...........................................................................................62
8.2.
Analysis Conventions.............................................................................................................................63
8.2.1.
Analysis Sets ........................................................................................................................63
8.3.
Data Handling Conventions ...................................................................................................................64
8.4.
Demographic Data and Baseline Characteristics ...................................................................................65
8.5.
Efficacy Analysis ...................................................................................................................................65
8.6.
Safety Analysis.......................................................................................................................................65
CCI

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8.6.1.
Extent of Exposure...............................................................................................................65
8.6.2.
Adverse Events.....................................................................................................................65
8.6.3.
Laboratory Evaluations ........................................................................................................66
8.6.4.
Other Safety Evaluations......................................................................................................66
8.7.
Pharmacokinetic Analysis......................................................................................................................66
8.8.
Biomarker Analysis................................................................................................................................66
8.9.
Sample Size............................................................................................................................................66
8.10.
Data Monitoring Committee ..................................................................................................................67
9.
RESPONSIBILITIES..........................................................................................................................................68
9.1.
Investigator Responsibilities ..................................................................................................................68
9.1.1.
Good Clinical Practice..........................................................................................................68
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (EC) 
Review and Approval...........................................................................................................68
9.1.3.
Informed Consent.................................................................................................................68
9.1.4.
Confidentiality......................................................................................................................69
9.1.5.
Study Files and Retention of Records ..................................................................................69
9.1.6.
Case Report Forms...............................................................................................................70
9.1.7.
Study Drug Accountability and Return ................................................................................71
9.1.8.
Inspections............................................................................................................................71
9.1.9.
Protocol Compliance............................................................................................................71
9.2.
Sponsor Responsibilities ........................................................................................................................72
9.2.1.
Protocol Modifications.........................................................................................................72
9.2.2.
Study Report.........................................................................................................................72
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................72
9.3.1.
Payment Reporting...............................................................................................................72
9.3.2.
Access to Information for Monitoring..................................................................................72
9.3.3.
Monitoring and Oversight of Biomarker Specimens............................................................72
9.3.4.
Access to Information for Auditing or Inspections ..............................................................73
9.3.5.
Study Discontinuation..........................................................................................................73
10.
REFERENCES ...................................................................................................................................................74
11.
APPENDICES ....................................................................................................................................................77
Appendix 1.
Investigator Signature Page....................................................................................................78
Appendix 2.
Study Procedures Table for GS-US-426-3989 .......................................................................79
Appendix 3.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................81
Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 ..........................83

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LIST OF IN-TEXT TABLES
Table 1-1.
Summary of Single Dose Pharmacokinetic Parameters of GS-0976 Following 
Administration of 30 mg to 1000 mg GS-0976 Under Fasting Conditions and 200 
mg GS-0976 Under Fed Conditions .......................................................................................20
Table 1-2.
Summary of Single and Multiple Dose Pharmacokinetic Parameters of GS-0976 
Following Administration of 50 mg BID, 100 mg QD, 100 mg BID, or 200 mg QD 
GS-0976 Under Fed Conditions .............................................................................................22
Table 1-3.
Summary of Single and Multiple Dose Pharmacokinetic Parameters of ND-011535 
Following Administration of 50 mg BID, 100 mg QD, 100 mg BID, or 200 mg QD 
GS-0976 Under Fed Conditions .............................................................................................23
Table 5-1.
List of Prohibited Medications ...............................................................................................38
LIST OF IN-TEXT FIGURES
Figure 3-1.
Overall Study Design .............................................................................................................29

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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study 
Evaluating the Safety, Tolerability, and Efficacy of GS-0976 in Subjects 
with Nonalcoholic Steatohepatitis
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
124915
Not Applicable
Not Available
Study Centers 
Planned:
Approximately 50 centers in the United States
Objectives:
The primary objective of this study is to evaluate the safety and 
tolerability of GS-0976 in subjects with nonalcoholic steatohepatitis 
(NASH) as assessed by magnetic resonance imaging-proton density fat 
fraction (MRI-PDFF) and magnetic resonance elastrography (MRE) or a 
historical liver biopsy consistent with NASH and non-cirrhotic fibrosis.
The exploratory objectives of this study are listed in Section 2.
Study Design:
This is a Phase 2 randomized, double-blind, placebo-controlled study 
evaluating the safety, tolerability, and biological activity of GS-0976 in 
subjects with NASH as assessed by MRI-PDFF and MRE, or a historical 
liver biopsy consistent with NASH and non-cirrhotic fibrosis.
Participation in the study can last up to approximately 22 weeks, which 
includes a 6-week Screening period, a 12-week treatment period during 
which study drugs will be administered, and a 4-week follow-up period.
The screening period may be extended under special circumstances with 
the explicit approval of the Medical Monitor.
Subjects meeting the study’s entry criteria will be randomly assigned in a 
2:2:1 ratio to 1 of 3 treatment groups as shown in the figure below:

GS-0976
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Study drugs will be administered for a total of 12 weeks. Randomization 
will be stratified by the presence or absence of diabetes mellitus as 
determined by medical history, use of medication for indication of 
diabetes mellitus, or based on Screening lab values if previously 
undiagnosed (i.e., hemoglobin A1c ≥ 6.5% OR fasting plasma 
glucose ≥126 mg/dL).
Number of 
Subjects 
Planned:
Approximately 125 subjects
Target 
Population:
Males and non-pregnant, non-lactating females between 18-75 years of 
age without cirrhosis and with NASH as assessed by MRI-PDFF and 
MRE or a historical liver biopsy consistent with NASH and non-cirrhotic 
fibrosis.
Duration of 
Treatment:
Subjects will be treated for 12 weeks.
Diagnosis and 
Main Eligibility 
Criteria:
Key inclusion and exclusion criteria are as follows:
Key Inclusion Criteria:

Meets the following conditions:
a) A clinical diagnosis of nonalcoholic fatty liver disease (NAFLD) with 
imaging or a liver biopsy documenting fatty liver within two years 
prior to Screening (if necessary, an ultrasound may be performed 
during Screening to confirm NAFLD), and 
b) Screening MRI-PDFF with ≥ 8% steatosis, and
c) Screening MRE with liver stiffness ≥ 2.5 kPa.  
Note: criterion a. must be met before evaluating criteria b. and c.
OR
tlQ 
C: ·c 
a, 
u 
Vl 
6 Weeks 
Group A (n=S0) 
GS-0976 5 mg+ 5 mg-PTM + 2 x 10 mg-PTM 
orally once daily 
Group B (n=S0) 
2 x GS-097610 mg+ 2 x 5 mg-PTM 
orally once daily 
Group C (n=25) 
2 x 5 mg-PTM + 2 x 10 mg-PTM 
orally once daily 
12 Weeks 
> 
"'C 
:::, 
ai 
0 
"'C 
C: 
I.LI 
--.... 
C. 
:::> 
15 
u.. 
4 
Weeks 

GS-0976
Protocol GS-US-426-3989
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
A historical liver biopsy within 12 months of Screening consistent 
with NASH (defined as the presence of steatosis, lobular 
inflammation, and hepatocellular ballooning) with fibrosis, but not 
cirrhosis, and

No documented weight loss > 5% between the date of the liver biopsy 
and Screening.

Platelet count ≥ 100,000/mm3

Creatinine Clearance (CLcr ) as calculated by the Cockcroft-Gault 
equation ≥ 60 ml/min
Key Exclusion Criteria:

Pregnant or lactating females;

ALT > 5 x ULN;

Other causes of liver disease including autoimmune, viral, and 
alcoholic liver disease;

Cirrhosis of the liver as defined by any of the following:
a) Cirrhosis on historical liver biopsy (e.g. NASH CRN classification
stage 4 or equivalent);
b) Evidence of cirrhosis on liver imaging (e.g. ultrasound, CT, or MRI) 
including a nodular liver surface, splenomegaly, or portal venous 
collaterals;
c) Prior history of decompensated liver disease, including ascites, 
hepatic encephalopathy or variceal bleeding;
d) Screening FibroSURE/FibroTest® ≥ 0.75, unless a historical liver 
biopsy within 12 months of Screening does not reveal cirrhosis. In 
patients with Gilbert’s syndrome or hemolysis, 
FibroSURE/FibroTest® will be calculated using direct bilirubin 
instead of total bilirubin. 

BMI < 18 kg/m2;

INR > 1.2, unless on anticoagulant therapy;

Total bilirubin > 1 x ULN, except with diagnosis of Gilbert’s 
syndrome;
Refer to Sections 4.2 and 4.3 for complete listing of inclusion and 
exclusion criteria.
Subjects with laboratory abnormalities outside of the above parameters 
may be approved for inclusion in the trial with approval from the Medical 
Monitor.

GS-0976 
Protocol GS-US-426-3989 
Gilead Sciences, Inc. 
Study 
Procedures/ 
Frequency: 
CONFIDENTIAL 
Final 
Amendment 1 
After signing the info1med consent fo1m, subjects will complete a 
Screening visit which will include the following assessments: complete 
medical histo1y, physical examination (PE), vital signs, laborato1y 
assessments (blood chemistiy, hematology, coagulation panel, 
hemoglobin Ale, and HIV-1, HBV, and HCV serology), sernm 
pregnancy test (for females of child-bearing potential), urine drng test, 
standard 12-lead ECG, ulti·asound (if necessa1y), review of adverse 
events, concomitant medications, and MRI-PDFF and MRE 
examinations. 
After the Screening period and a randomization visit at Baseline/Day 1, 
study visits will occur on Weeks 1, 4, 8, 12, and a Follow-Up visit 4 
weeks after the last dose of study diugs. At minimum, vital signs, 
symptom di·iven PE, safety laborato1y tests (blood chemistiy, 
hematology, coagulation panel, and lipid profile), review of adverse 
events and concomitant medications will be done at eve1y visit. 
Eligible subjects will be randomized to one of 3 ti·eatment groups. Prior 
to initial dosing, required Baseline/Day 1 assessments will be perfo1med 
and will include symptom di·iven PE, vital signs (including waist 
circumference), laborato1y assessments, pregnancy tests (for females of 
child-bearing potential), urine, blood, and stool collection for biomarker 
assessment, Quality of Life (QoL) questionnaires, standard 12-lead ECG, 
FibroScan® (if available), review of adverse events and concomitant 
medications. 
While on study, subjects will undergo the following procedures and 
laborato1y assessments: 
• 
MRE and MRI-PDFF at Week 12 
• 
FibroScan® at Baseline/Day 1 and Week 12 (if available) 
• 
Single PK sampling at Weeks 1, 4, 8, and 12 
• 
Blood collection for Biomarkers at Baseline/Day 1, and at Weeks 1, 
4, and 12 
• 
Urine collection for Biomarkers at Baseline/Day 1, and at Weeks 1, 4, 
and 12 
• 
12-lead ECGs at Baseline/Day 1 and Week 12 
• 
Hematology, blood chemistiy, fasting lipid profile, PT, PTT, and INR 
at Baseline/Day 1, and at Weeks 1, 4, 8, 12, and Follow-Up visit 
• 
Hemoglobin Ale (HbAle) at Baseline/Day 1 and Week 12 
• 
Stool collection for Biomarkers at Baseline/Day 1 and Week 12 
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15 December 2016 

GS-0976 
Protocol GS-US-426-3989 
Gilead Sciences, Inc. 
Test Product, Dose, 
and Mode of 
Administration: 
Reference Therapy, 
Dose, and Mode of 
Administration: 
Criteria for 
Evaluation: 
Safety: 
CONFIDENTIAL 
Final 
Amendment 1 
• 
Urine pregnancy test (females of childbearing potential only) at 
Baseline/Day 1, and at Weeks 4, 8, 12, and Follow-Up visit 
• 
SF-36, WPAI, and CLDQ at Baseline/Day 1 and Week 12 
Subjects will return for their final visit, the Follow-Up visit, 4 weeks after 
the last dose of study chu gs. At this visit assessments include a symptom 
driven PE, vital signs, review of concomitant medications and AEs, and 
safety laborato1y tests. A urine pregnancy test will be perfonned for 
females of child bearing potential only. 
• 
Treatment Group A: GS-0976 5 mg (1 x 5 mg capsule, 1 x 5 mg-PTM 
capsule, 2 x 10 mg-PTM capsules) administered orally once daily; 
n=50 subjects 
• 
Treatment Group B: GS-0976 20 mg (2 x 10 mg capsule, 
2 x 5 mg-PTM capsules) administered orally once daily; 
n=50 subjects 
• 
Treatment Group C: GS-0976 Placebo (2 x 5 mg-PTM capsules, 
2 x 10 mg-PTM capsules) achninistered orally once daily; 
n=25 subjects 
Placebo-to-match 5 mg (5 mg-PTM) GS-0976 capsules and 
placebo-to-match 10 mg capsules (10 mg-PTM) are identical in size, 
shape, color and appearance to their conesponding strengths of active 
GS-0976 capsules. 
The primaiy endpoint is the safety of GS-0976 in subjects with NASH. 
Safety will be assessed during the study through the repo1t ing of AEs, 
and by clinical laborato1y tests and vital sign assessments at various time 
points during the study. Concoinitant medication usage will also be 
assessed throughout the study. 
An independent, external Data Monitoring Cominittee (DMC) that 
consists of two hepatologists and a PhD statistician will convene once 
20 subjects have been randoinized and eve1y 3 to 4 months thereafter to 
monitor the study for safety events. The DMC will meet on an ad hoc 
basis if there are at least 3 siinilar Grade 
3 serious, treatment related 
Common Tenninology Criteria for Adverse Events (CTCAE) observed in 
the trial. In the event of two siinilar Grade 4-CTCAE treatment related 
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15 December 2016 

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events or one Grade 5-CTCAE treatment related event, the DMC will 
review the data and advise the sponsor regarding stopping or continuing 
the trial.
Efficacy:
Efficacy will be assessed through a number of exploratory endpoints. 
These exploratory endpoints are described in Section 8.1.3.
Pharmacokinetics:
A single PK blood sample will be collected at each on-treatment visit for 
all subjects. Plasma concentrations of GS-0976, and other metabolites as 
appropriate, will be determined for PK analyses as applicable.
Statistical 
Methods:
Safety Analysis:
All safety data collected will be listed and summarized, as appropriate, by 
treatment group.
Efficacy 
Analysis:
The biological activity of GS-0976 will be evaluated using biomarker 
variables. Because efficacy endpoints will be evaluated for exploratory 
purpose, formal statistical comparisons will not be made for these 
endpoints. Ninety-five percent confidence intervals (95% CI) will be 
provided if applicable.
Exploratory 
Analysis:
Point estimates and 95% CI will be calculated for all continuous 
exploratory parameters (e.g. MRI-PDFF, MRE, FibroScan®). For 
categorical variables, descriptive statistics will be calculated with count 
and percentage of subjects in each category by treatment group.
Sample Size:
Due to the exploratory nature of this study, no formal power calculations 
were used to determine sample size. The number of subjects was chosen 
based on clinical experience with other similar proof of concept studies.
This study will be conducted in accordance with the guidelines of Good Clinical Practices 
(GCPs) including archiving of essential documents.

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C
degrees Celsius
F
degrees Fahrenheit
ACC
acetyl-CoA carboxylases
AE
adverse event
ALP
alkaline phosphatase 
ALT
alanine aminotransferase
Apo B
apolipoprotein B
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
AUC0-last
area under the plasma concentration-time curve from time 0 to the last 
measurable concentration
AUCinf
area under the plasma/serum/PBMC concentration versus time curve 
extrapolated to infinite time, calculated as AUC0-last + (Clast/λz)
AUCpartial
partial area under the plasma/serum concentration versus time curve
AUCtau
area under the plasma/serum/PBMC concentration versus time curve over the 
dosing interval
AUROC
area under the receiver operating characteristic curve
BAP
Biomarker Analysis Plan
BID
twice a day
BMI
body mass index
BUN
blood urea nitrogen
BW
body weight
C4
7-alpha-hydroxy-4-cholesten-3-one
CFR
Code of Federal Regulations
CI
confidence interval
CK-18
cytokeratin 18
CLDQ
Chronic Liver Disease questionnaire
CL/F
apparent oral clearance
CLcr
creatinine clearance
CLrenal
Renal clearance 
Clast
last observed quantifiable serum/plasma/PBMC concentration of the drug
Cmax
maximum observed concentration of drug
Cmin
minimum observed plasma/serum concentration of drug
CRO
contract (or clinical) research organization
CSR
clinical study report
CT
computed tomography
Ctau
observed drug concentration at the end of the dosing interval
CTCAE
Common Terminology Criteria for Adverse Events
CYP
cytochrome P450

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CYP3A
cytochrome P4503A
DILI
drug induced liver injury
dL
deciliter
DMC
Data Monitoring Committee
DNL
de novo lipogenesis
DSPH
Drug Safety and Public Health
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form(s)
EDC
electronic data capture
ELF™Test
enhanced liver fibrosis test
ESA
erythropoiesis-stimulating agent
eSAE
electronic serious adverse event
eSSR
electronic special situations report
ET
early termination
EU
European Union
FAS
Full Analysis Set
FDA
(United States) Food and Drug Administration
FGF19
fibroblast growth factor 19
FSH
follicle stimulating hormone
GCP
Good Clinical Practice (Guidelines)
GCSF
granulocyte colony stimulating factor
GGT
gamma glutamyl transferase
Hb
hemoglobin
HbA1c
hemoglobin A1c
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCC
hepatocellular carcinoma
hCG
human chorionic gonadotropin
Hct
hematocrit
HCV
hepatitis C virus
HCV Ab
hepatitis C antibody
HDPE
high density polyethylene
HIV
human immunodeficiency virus
HIV-1
human immunodeficiency virus type 1
HLGT
high-level group term
HLT
high-level term
HOMA-IR
homeostatic assessment of insulin resistance
HRQoL
health related quality of life
IB
Investigator Brochure

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ICF
Informed Consent Form
ICH
International Conference on Harmonisation
ID
Identification
IEC
independent ethics committee/ institutional ethics committee
IND
Investigational New Drug (Application)
INR
international normalized ratio
IRB
institutional review board
IUD
intrauterine device
IWRS
interactive web response system
kg
kilogram
LDH
lactate dehydrogenase
LLT
lower-level term
MAD
multiple ascending dose
MCV
mean corpuscular volume
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram
miRNA
micro ribonucleic acid
mmHg
millimeters of mercury
MPR
metabolite-to-parent
MRE
magnetic resonance elastography
MRI
magnetic resonance imaging
MRI-PDFF
magnetic resonance imaging – proton density fat fraction
NAFLD
nonalcoholic fatty liver disease
NASH
nonalcoholic steatohepatitis
NMR
nuclear magnetic resonance spectroscopy
NOEL
no-observed--effect-level
NOAEL
no observed adverse event level
N/C
not calculated
OATP
organic anion-transporting polypeptide
oz
ounce
PE
physical exam
PG
pharmacogenomics(s)
P-gp
P-glycoprotein
PK
pharmacokinetic(s)
PT
preferred term
PT
prothrombin time
PTM
placebo-to-match
PTT
partial prothrombin time
QD
once daily
QoL
quality of life

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QT
electrocardiographic interval between the beginning of the Q wave and 
termination of the T wave representing the time for both ventricular 
depolarization and repolarization to occur
RAUC
Ratio of Day 10 AUC0-tau / Day 1AUC0-t
RBC
red blood cell count
RNA
ribonucleic acid
ROS
reactive oxygen species
SADR
serious adverse drug reaction
SAE
serious adverse event 
SAP
Statistical Analysis Plan
SD
standard deviation
SF-36
Short Form (36) Health Survey
SOC
System Organ Class
SOP
standard operating procedure
SSR
special situations report
SUSAR
Suspected Unexpected Serious Adverse Reaction
TEAE
treatment-emergent adverse event
Tmax
the time (observed time point) of Cmax
T1/2
an estimate of the terminal elimination half-life of the drug in, calculated by 
dividing the natural log of 2 by the terminal elimination rate constant (λz)
TPO
Thrombopoietin
ULN
Upper limit of the normal range
US
United States
Vz/F
apparent volume of distribution of the drug
WBC
White blood cell count
WHO
World Health Organization
WPAI
Work Productivity and Activity Impairment

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1.
INTRODUCTION
1.1.
Background
Chronic liver disease and the consequences of end-stage liver disease are increasing globally 
despite improved prevention and treatment of viral hepatitis. This is due to the emerging 
epidemics of obesity, metabolic syndrome, and diabetes mellitus that are leading to an increased 
incidence of nonalcoholic fatty liver disease (NAFLD). Nonalcoholic fatty liver disease is 
characterized by the excess accumulation of lipid droplets within the liver, also known as hepatic 
steatosis. Prevalence rates of NAFLD range from 6% to 37% worldwide {Ong 2007, Vernon 
2011}. Nonalcoholic steatohepatitis (NASH), an aggressive form of NAFLD characterized by 
the presence of inflammation and hepatocellular ballooning, with or without fibrosis, is present 
in approximately 25% of patients with NAFLD. Nonalcoholic steatohepatitis is associated with 
increased liver-related mortality {Ong 2007, Williams 2011}. In the United States (US), it has 
been estimated that 3% to 6% of the population, {Vernon 2011, Wanless 1990}, or the 
equivalent of up to 15 million adults, have NASH. NASH represents a significant and growing 
unmet medical need for which there are no currently approved therapies. Furthermore, as NASH 
is a manifestation of the metabolic syndrome, risk factors for cardiovascular disease 
(eg, atherosclerotic disease, cardiac arrhythmogenicity) frequently coexist in these patients 
{Dietrich 2014, Faramawi 2008, Voulgari 2010}. A treatment that targets the underlying 
metabolic disorder could potentially ameliorate these cardiovascular risks and associated 
morbidity and mortality.
Nonalcoholic steatohepatitis is primarily thought to occur as the result of the metabolic 
syndrome, the impact of obesity, insulin resistance, and dyslipidemia in the liver. Simple 
steatosis is not sufficient to cause liver injury; it is the presence of inflammation and 
hepatocellular injury on the background of steatosis that defines NASH and results in the 
progression to end-stage liver disease and its complications. The “2-hit” hypothesis of NASH 
suggests that in the setting of steatosis and metabolic dysfunction, increased oxidative stress and 
the generation of reactive oxygen species (ROS) likely mediate the inflammatory changes in the 
liver (steatohepatitis) that may lead to progressive fibrosis {Dowman 2010, Kannel 1982, Koek 
2011, Sumida 2013}. The major pathways in NASH disease progression include those involved 
in metabolic dysfunction in the hepatocyte, and activation of hepatic stellate cells and 
macrophages leading to progressive inflammation and liver fibrosis. Advanced fibrosis and 
cirrhosis are characterized by extensive collagen deposition and remodeling of the extracellular 
matrix. In addition, evidence suggests that lipotoxic intermediates of fatty acids likely contribute 
to the etiology of NASH {Neuschwander-Tetri 2010}.  
Over time, NASH may result in progressive liver fibrosis, ultimately leading to cirrhosis in 
10-20% of affected patients. Advanced fibrosis (bridging fibrosis or cirrhosis) is associated with 
increased morbidity and mortality {Ekstedt 2015, Yeh 2014}. Patients with cirrhosis may 
develop hepatocellular carcinoma (HCC) and other complications of end-stage liver disease, 
including jaundice, fluid retention (edema and ascites), portal hypertension and variceal 
bleeding, impaired coagulation and hepatic encephalopathy. Decompensated liver disease, as 

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defined by the development of one of the above complications, has a high mortality and the only 
known effective treatment is liver transplantation. With the increasing prevalence of obesity and 
obesity-related diseases, NASH is expected to become the leading indication for liver
transplantation, and the leading etiology of HCC among liver transplant recipients in the US 
{Afzali 2012, Wong 2014}.
1.2.
GS-0976
GS-0976 is a small molecule allosteric inhibitor that acts at the protein-protein homodimer 
interface of acetyl coenzyme A (acetyl-CoA) carboxylases (ACC) ACC1 and ACC2, to prevent 
dimerization. ACC1 and ACC2 are important regulators of fatty acid metabolism. ACC1 
catalyzes the first step of de novo lipogenesis (DNL) by converting acetyl-CoA to malonyl-CoA 
while ACC2 regulates the entry of fatty acids into the mitochondria where beta oxidation can 
occur. Therefore, inhibition of ACC1 and ACC2 will reduce DNL and increase fatty acid beta 
oxidation. GS-0976 is being developed for the treatment of NASH.
1.2.1.
General Information
For further information on GS-0976, refer to the current Investigator Brochure (IB) for GS-0976.
1.2.2.
Nonclinical Pharmacology
GS-0976 has been characterized in several biochemical and cellular assays to enhance the 
understanding of the mechanism of action and has been well characterized in vivo in several 
mechanistic models to demonstrate target engagement and in animal disease models to 
demonstrate specific activity on endpoints relevant to metabolic disease. Moreover, extensive 
safety pharmacology and receptor screening studies have been conducted.
The results of these pharmacodynamic (PD) studies indicate that GS-0976 can favorably affect 
the DNL, hepatic steatosis, insulin resistance, and body weight/body fat elevations produced in 
nonclinical models of metabolic disease without affecting food consumption or markers of liver 
function. In total, these studies confirm the potential for GS-0976 to impact important metabolic 
endpoints associated with NASH.
1.2.3.
Nonclinical Toxicology
The toxicity of GS-0976 was evaluated in rats and dogs in acute and repeated dose nonclinical 
studies up to 13 weeks in duration. Selection of the test species was based on the in vitro and in 
vivo assessment of metabolism. In in vitro experiments using human hepatocytes, 
no human-specific metabolites were identified and all metabolites detected were also present in 
rat and/or dog hepatocytes.
There were no adverse findings in safety pharmacology studies (central nervous system, 
respiratory and cardiovascular studies) at exposures ~ 50 fold above the predicted steady-state 
clinical exposure (Cmax ~110 ng/mL) after administration of 20 mg GS-0976 once daily (QD) 
fasted. The genotoxicity potential of GS-0976 was considered low as the compound is negative 
in the in vitro Ames, chromosome aberration studies and the in vivo mouse micronucleus study.

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Single doses of GS-0976 up to 1000 mg/kg were tolerated in rats and dogs. In the 28-day studies, 
the no-observed-adverse-effects levels (NOAELs) for the rat and dog were 60 and 
100 mg/kg/day respectively, the highest doses tested in the studies, affording exposure margins 
of at least 23 (rat) and 63 (dog) times above the predicted steady-state clinical exposure after 
administration of 20 mg GS-0976 QD fasted (240 ng•h/mL). In the 13-week rat study, no dose 
limiting toxicity was observed and the NOAEL was 60 mg/kg/day, the highest dose tested, 
providing an exposure margin of 23-fold above predicted steady-state clinical exposure. In the 
13-week dog study, bilateral posterior cortical cataracts and histological evidence of cataracts
were observed at 90 mg/kg/day, with progression in severity after a 28-day recovery period. 
There was no evidence of cataracts at doses ≤30 mg/kg/day. In the 13-week dog study, the 
presence of cataracts was found at exposures approximately 82 times above the predicted 
steady-state clinical exposure. No evidence of cataracts was observed at doses ≤ 30 mg/kg/day. 
The NOAEL for the 13-week dog study was 30 mg/kg/day, providing an exposure margin of 
approximately 15 fold above the predicted steady-state clinical exposure at 20 mg.
In the rat embryo-fetal development dose-range finding study, maternal toxicity and fetal 
abnormalities (external and soft tissue malformations, and developmental variations) were 
observed at doses ≥ 50 mg/kg/day in a dose-dependent manner. The no-observed-effect level 
(NOEL) for the embryo-fetal rat study was 25 mg/kg/day at an approximate exposure margin of
5.8 times above the predicted steady-state clinical exposure. In the rabbit study, 100 mg/kg/day 
was not tolerated and maternal toxicity (decreased body weight gain and food consumption) was 
observed at doses ≥ 25 mg/kg/day. While decreases in fetal weights were observed at doses 
≥10 mg/kg/day, no external malformations and developmental variations were observed at all 
doses.  The NOEL for the embryo-fetal rabbit study was less than 10 mg/kg/day. At this dose, 
the predicted steady-state clinical exposure margin is approximately 53. The observed 
embryo-fetal effects were not unexpected as the deletion of ACC1 in mice is embryonically 
lethal.
1.2.4.
Nonclinical Pharmacokinetics
GS-0976 is highly protein bound in plasma, and the volume of distribution of GS-0976 across 
nonclinical species is greater than total body water (0.7 L/kg), suggesting that GS-0976 is well 
distributed. A significant fraction of the absorbed parent compound is extracted by the liver 
indicating that GS-0976 is available to the target site (ie, the liver).
The metabolism of GS-0976 has been evaluated in in vitro incubations of rat, dog, Cynomolgus 
monkey, and human hepatocytes. No metabolites unique to the human were detected. In vivo 
metabolite identification studies in Sprague-Dawley rat and Beagle dog have demonstrated that 
the primary metabolite of GS-0976 is the glucuronide conjugate.
Neither GS-0976 nor the metabolite, NDI-011535, inhibits the cytochrome P450 (CYP) enzymes 
involved in drug metabolism. GS-0976 is not an inducer of CYP1A2 or CYP2B6 isozymes and 
is a mild inducer of CYP 3A4 in human hepatocytes in vitro.

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A single nonclinical study to evaluate elimination of GS-0976 and the metabolite NDI-011535 
was performed in bile duct cannulated Sprague-Dawley rats to profile concentrations over time 
in plasma, urine, and bile. Overall, the pharmacokinetic (PK) profile in plasma and bile indicate 
that GS-0976 is rapidly cleared from the plasma compartment, and the primary route of 
elimination is via the bile.
1.2.5.
Clinical Trials of GS-0976 
1.2.5.1.
Study 0976-101: Single Ascending Dose (SAD) Study
The first-in-human single ascending dose (SAD) study (Protocol Number 0976-101) was a 
randomized, placebo-controlled, double-blind study performed in normal, healthy adult subjects 
at one study center in the United States with a starting dose of 30 mg. The dosing in this study is 
completed with PK and tolerability data obtained following dosing of 30, 80, 200, 500, 800, and 
1000 mg in the fasted state and 200 mg following a high fat meal (fed state) to cohorts of 
8 subjects (6 active and 2 placebo control per group). Final data from the SAD study indicated 
that single doses of GS-0976 were tolerated across the dose range of 30 to 1000 mg. There were 
no deaths, serious adverse events (SAEs), or subject discontinuations due to adverse events 
(AEs) in this study. There were no clinically important treatment related or dose related trends in 
the incidence or severity of treatment emergent adverse events (TEAEs), clinical laboratory, vital 
sign, ECG, or physical examination assessments in this study. Abdominal discomfort, vessel 
puncture site pain, dizziness, and presyncope, reported by 2 subjects each (6% overall for fasted 
GS-0976), were the most frequently reported events in this study. Of the 27 TEAEs reported in 
the study, all were of Grade 1 severity. The principal investigator considered 2 TEAEs to be 
probably related (1 episode each of nausea and dyspepsia in placebo fasted subjects), 4 possibly 
related (1 episode of cough in the 30 mg GS-0976 fasted group and 1 episode each of discolored 
feces, abdominal discomfort, and diarrhea in the 500 mg GS-0976 fasted group), and 
21 unrelated to study treatment. 
Pharmacokinetic parameters of GS-0976 are presented in Table 1-1. Plasma GS-0976 maximum
plasma concentration (Cmax) and overall exposure (AUCinf) generally increased in a dose 
proportional manner across the range of 30 to 500 mg, under fasted conditions, with greater than 
dose-proportional increases above 500 mg. Similar results were observed for plasma 
NDI-011535 (glucuronide metabolite of GS-0976). The apparent total body clearance (CL/F) and 
apparent volume of distribution (Vz/F) of GS-0976 decreased with increasing GS-0976 doses of 
800 mg and 1000 mg. Urinary excretion of unchanged GS-0976 was negligible. GS-0976 Cmax
was approximately 68% lower under fed compared to fasted conditions; however, overall plasma 
GS-0976 exposure (based on AUC0-t and AUC0-inf) was only approximately 9% to 14% lower 
under fed compared to fasted conditions, which may not be a clinically significant difference. 
The median Tmax and mean T1/2 values were similar under fed and fasted conditions, although
there was a delay in the first quantifiable concentration and a prolonged absorption/distribution 
phase observed under fed compared to fasted conditions. Similar results were observed for 
plasma NDI-011535. Mean plasma NDI-011535 exposure was < 10% of GS-0976 plasma 
exposure, based on metabolite-to-parent (MPR) Cmax and MPR AUCinf.

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Table 1-1.
Summary of Single Dose Pharmacokinetic Parameters of GS-0976 
Following Administration of 30 mg to 1000 mg GS-0976 Under
Fasting Conditions and 200 mg GS-0976 Under Fed Conditions
PK 
Parameter
Mean + SD
GS-0976 Dose (mg)
30 mg
Fasted
(N=6)a
80 mg
Fasted
(N=6)a
200 mg
Fasted
(N=6)a
200 mg
Fed
(N=6)a
500 mg
Fasted
(N=6)b
800 mg
Fasted
(N=6)b
1000 mg
Fasted
(N=6)
Plasma
AUC0-t
(ng*h/mL)
176 + 104
363 + 215
1210 + 537
1160 + 613
2930 +
2440
6420 + 3180
17,400 +
8400
AUC0-inf
(ng*h/mL)
179 + 115
402 + 225
1250 + 616
1260 + 683
2960 +
2460
6460 + 3190
17,500 +
8410
Cmax
(ng/mL)
79.7 + 65.9
101 + 47.8
416 + 211
134 + 70.1
1110 +
1150
2570 + 1880
8380 + 3210
Tmax (h)c
1.26 
(0.23, 2.00)
2.00 
(1.50, 2.00)
1.50 
(1.01, 4.00)
2.00 
(1.50, 24.0)
1.75 
(1.01, 3.00)
2.01 
(1.01, 3.00)
2.50 
(1.02, 4.01)
T1/2 (h)
4.47 + 1.56
6.98 + 2.81
11.7 + 1.35
8.70 + 2.10
10.2 + 2.13
8.24 + 3.26
9.46 + 2.60
CL/F (L/h)
250 + 178
251 + 124
189 + 76.5
212 + 131
290 + 188
146 + 57.4
65.2 + 21.3
Vz/F (L)
1730 +
1510
2360 +
1390
3150 +
1270
2500 +
1290
4190 +
2570
1620 + 561
904 + 469
Urine
Ae0-48 (µg)
9.72 + 8.73
25.8 + 11.7
48.8 + 21.3
N/C
135 + 106
1030 + 924
636 + 600
Fe (%)
0.032 +
0.029
0.032 +
0.015
0.024 +
0.011
N/C
0.027 +
0.021
0.129 +
0.115
0.064 +
0.060
CLRenal
(mL/h)
50.0 + 45.1
109 + 96.2
46.2 + 15.5
N/C
77.5 + 65.7
135 + 62.2
42.6 + 36.5
PK parameters are presented to 3 significant digits, N/C = Not Calculated
a
N=5 for AUC0-inf, T1/2, CL/F, and Vz/F
b
N=5 for Ae0-48, Fe, and CLrenal
c
Tmax is presented as median (minimum, maximum)
The Ae0-48, Fe, and Clrenal for subject 
 (500 mg GS-0976) were missing, because this subject was unable to provide urine 
samples during the 12-24 hour, 24-36 hour, and 36-48 hour intervals, due to an AE.
The Ae0-48, Fe, CLrenal for subject 
 (800 mg GS-0976) were excluded from the summary statistics, because the urine sample 
for the 24-36 hour collection interval was partially spilled prior to volume measurement (ie, calculations were based off an 
approximate urine volume)
1.2.5.2.
Study 0976-102: Multiple Ascending Dose (MAD) Study
The multiple ascending dose (MAD) study (Protocol Number 0976-102) was a randomized, 
double-blind, placebo-controlled, clinical study conducted in healthy adult subjects at one study 
center in the United States. Five (5) cohorts of 8 subjects (6 active and 2 placebo) were evaluated 
at the following GS-0976 doses: 50 mg BID (100 mg daily) or placebo, 100 mg QD (100 mg 
daily) or placebo, 100 mg BID (200 mg daily) or placebo, 200 mg QD (200 mg daily) or 
placebo, or 150 mg QD (150 mg daily) or placebo. In each cohort, subjects received multiple 
PPD
PPD--

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oral doses of GS-0976 or placebo BID (every 12 hours) or once daily (QD) for 9 consecutive 
days (Days 1 through 9), with a single oral dose of GS-0976 or placebo on the morning of 
Day 10. Doses were administered approximately 30 minutes after meals. Preliminary safety and 
PK data are available for the first 4 dose groups. 
Each of the first 4 dose groups was fully enrolled and, overall, 24 subjects received GS-0976 and 
8 subjects received placebo. The majority of these 32 subjects who received GS-0976 (19/24, 
79%) and placebo (4/8, 50%) had at least 1 treatment-related AE as assessed by the principal 
investigator. The incidence of treatment-related AEs appeared to increase with higher doses and 
BID dosing of GS-0976: 50% of subjects at 50 mg BID, 62.5% at 100 mg QD, 75% at 200 mg 
QD, and 100% at 100 mg BID. One subject in the 200 mg QD cohort discontinued due to an AE 
on study Day 7 for Grade 4 elevated triglycerides (TG). No deaths or SAEs were reported. 
The most frequently reported TEAEs were gastrointestinal disorders and involved nausea 
(33% of all subjects who received GS-0976 vs. 0% of all subjects who received placebo), 
abdominal distension (25% GS-0976 vs. 13% placebo), constipation 
(21% GS-0976 vs. 13% placebo), diarrhea (21% GS-0976 vs. 0% placebo), and vomiting 
(13% GS-0976 vs. 0% placebo). In addition, TEAEs of increased blood triglycerides were 
reported (25% GS-0976 vs. 0% placebo) and involved Grade 3 events in 5 subjects (3 subjects in 
the 100 mg BID cohort and 2 subjects in the 50 mg BID cohort), and a Grade 4 event in 1 subject 
in the 200 mg QD cohort (discontinued treatment).
There were no clinically important treatment-related or dose-related trends in vital signs, ECG, 
or physical examination assessments in this study.
Preliminary single (Day 1) and (Day 10) multiple dose PK parameters for GS-0976 and 
ND-011535 after administration of 50 mg BID, 100 mg QD, 100 mg QD, and 200 mg QD 
GS-0976 under fed conditions are presented Tables 1-2 and 1-3, respectively. In general, 
GS-0976 AUC and Cmax increased in a dose proportional manner across the doses evaluated.  
GS-0976 AUC accumulated approximately 2-fold on Day 10 compared to Day 1 with minimal 
accumulation of Cmax.  Median GS-0976 Tmax occurred between 3 and 6 hours, in agreement with 
the food effect observed in study 0976-101.  The mean T1/2 of GS-0976 ranged from 
3.5-10.3 hours with higher variability contributing to the higher mean estimates from Day 10 in 
the 50 mg BID and 100 mg QD cohorts.  Mean plasma NDI-011535 exposure was < 10% of 
GS-0976 plasma exposure, based on MPR for AUC and Cmax.  The PK profile of NDI-011535 
was consistent with the PK profile of GS-0976, as seen by the consistent MPR for AUCinf and 
Cmax on Day 1 and Day 10 as well as across the doses evaluated. NDI-011535 exhibits formation 
rate limited kinetics as the mean T1/2 of NDI-011535 was consistent with that observed for 
GS-0976.

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Table 1-2.
Summary of Single and Multiple Dose Pharmacokinetic Parameters 
of GS-0976 Following Administration of 50 mg BID, 100 mg QD, 
100 mg BID, or 200 mg QD GS-0976 Under Fed Conditions
Plasma PK Parameter
Mean + SD
GS-0976 Dose
50 mg BID Fed 
(N=6)
100 mg QD Fed 
(N=6)
100 mg BID Fed 
(N=6)
200 mg QD Fed 
(N=6)
Day 1
AUC0-12or24 (ng*h/mL)
143 + 29.1
268 + 95.7
345 + 77.0
868 + 221
AUC0-inf (ng*h/mL)
178 + 40.7a
278 + 110a
671b
979 + 286a
Cmax (ng/mL)
41.3 + 14.3
64.9 + 31.7
61.6 + 14.7
152 + 68.4
Tmax (h)c
2.50 (1.50, 3.02)
3.50 (1.00, 6.00)
5.02 (3.00, 8.00)
5.00 (2.00, 6.00)
T1/2 (h)
3.50 + 1.63a
4.33 + 0.741a
5.58b
5.86 + 3.59a
CL/F (L/h)
292 + 61.6a
403 + 139a
149b
219 + 64.0a
Vz/F (L)
1350 + 333a
2560 + 1180a
1120b
1710 + 720a
Day 10
AUC0-tau (ng*h/mL)
305 + 77.0
369 + 160
742 + 217
1770 + 573a
RAUC
2.13 + 0.279
1.37 + 0.323
2.23 + 0.766
2.10 + 0.636a
Cmax (ng/mL)
49.4 + 15.2
53.5 + 22.4
121 + 56.3
198 + 86.6a
Cave (ng/mL)
25.4 + 6.42
15.4 + 6.68
61.8 + 18.1
73.7 + 23.9a
Ctrough (ng/mL)
12.4 + 5.04
3.16 + 2.24
56.1 + 22.7
33.9 + 42.9a
Tmax (h)c
4.01 (2.05, 8.00)
3.01 (2.00, 12.0)
6.00 (2.00, 6.00)
4.00 (1.50, 6.00)a
T1/2 (h)
10.3 + 6.66
7.92 + 4.52
6.83 + 1.62
5.91 + 0.987a
CLss/F (L/h)
173 + 41.5
312 + 116
145 + 43.5
125 + 46.4a
PK parameters are presented to 3 significant digits
RAUC = Ratio of Day 10 AUC0-tau / Day 1 AUC0-t
a
N=5
b
N=1
c
Tmax is presented as median (minimum, maximum)

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Table 1-3.
Summary of Single and Multiple Dose Pharmacokinetic Parameters 
of ND-011535 Following Administration of 50 mg BID, 100 mg QD, 
100 mg BID, or 200 mg QD GS-0976 Under Fed Conditions
Plasma PK Parameter 
Mean + SD
GS-0976 Dose
50 mg BID Fed 
(N=6)
100 mg QD Fed 
(N=6)
100 mg BID Fed 
(N=6)
200 mg QD Fed 
(N=6)
Day 1
AUC0-12or24 (ng*h/mL)
11.6 + 3.57a
23.7 + 0.891b
29.9 + 15.1a
78.8 + 43.3c
MPR AUC
0.064 + 0.022c
0.042d
0.063 + 0.027a
0.0636 + 0.027c
Cmax (ng/mL)
3.14 + 1.39
3.98 + 2.29
4.36 + 2.63
9.54 + 6.66
MPR Cmax
0.057 + 0.013
0.051 + 0.023
0.054 + 0.028
0.048 + 0.020
Tmax (h)e
2.50 (1.50, 302)
3.50 (1.50, 6.00)
6.00 (4.00, 11.9)
6.00 (4.00, 6.00)
T1/2 (h)
5.13 + 2.93a
3.59 + 0.895b
N/C
7.55 + 2.06c
Day 10
AUC0-tau (ng*h/mL)
28.5 + 8.89
46.0 + 22.6f
67.0 + 31.6
129 + 74.3a
RAUC
2.49 + 0.32a
2.50 + 0.150b
1.93 + 0.752a
2.41 + 1.03f
MPR AUC
0.072 + 0.013
0.073 + 0.015 N=3
0.050 + 0.020
0.052 + 0.016a
Cmax (ng/mL)
4.92 + 1.90
4.52 + 3.82
6.62 + 2.84
12.2 + 5.33a
Cave (ng/mL)
2.37 + 0.741
1.92 + 0.943f
3.95 + 1.64
5.38 + 3.09a
MPR Cmax
0.075 + 0.014
0.057 + 0.028
0.046 + 0.019
0.051 + 0.02a
Ctrough (ng/mL)
1.20 + 0.383
0.575 + 0.078b
3.76 + 1.45
3.21 + 3.18c
Tmax (h)e
3.50 (2.05, 6.00)
4.51 (2.00, 6.02)
6.00 (1.50, 6.04)
6.00 (3.00, 6.00)a
T1/2 (h)
4.61 + 1.30a
6.00 + 0.225b
5.67 + 0.40b
5.14 + 2.14f
PK parameters are presented to 3 significant digits
RAUC = Ratio of Day 10 AUC0-tau / Day 1 AUC0-t
MPR = Metabolite to Parent Ratio corrected for molecular weight
N/C = Not Calculated
a
N=5
b
N=2
c
N=4
d
N=1
e
Tmax and T1/2 are presented as median (minimum, maximum)
f
N=3
1.2.5.3.
Study 0976-103: Single Ascending Dose Pharmacodynamic Study
The single ascending dose PD study (Study 0976-103) was a two-period, two-treatment, 
crossover, randomized, double-blind, study to determine the PD activity on fractional DNL of a 
single oral dose of 20, 50, or 200 mg of GS-0976 compared to placebo in 3 cohorts of 10 adult 
male subjects who were overweight and/or obese, but otherwise healthy, at each dose level (total 
30 subjects). Subjects were randomized in Period 1 to receive a single oral dose of either 

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GS-0976 or matched placebo followed by a washout and administration of the opposite study 
medication in Period 2. 
The objectives of the study were to assess the following after a single oral dose of GS-0976 in 
overweight and/or obese, but otherwise healthy, adult male subjects: PD effects of GS-0976 on 
fractional DNL, safety and tolerability of GS-0976, correlation of PK and PD effects, and PK 
parameters. 
Fractional DNL was evaluated by utilizing a qualified method that measured the appearance of 
de novo synthesis of palmitate in very-low density lipoproteins (VLDL) in response to oral 
fructose using [13C] acetate incorporation into palmitate and mass isotopomer distribution 
analysis (MIDA). Review of the data demonstrated mean inhibition of fractional DNL (71%, 
87%, and 98% by AUC) by GS-0976 at 20, 50, and 200 mg, respectively, compared to matched 
placebo.
A total of 41 TEAEs were experienced by 15 (52%) subjects following administration of 
GS-0976 (28 considered possibly related); 22 TEAEs were experienced by 12 (40%) pooled 
placebo subjects (17 considered possibly related), and 4 TEAEs were experienced by 4 (13%) 
subjects following the [13C] acetate infusion. Gastrointestinal events including diarrhea (11/29, 
38% GS-0976 vs. 9/30, 30% placebo) and flatulence (5/29, 17% GS-0976 vs. 3/30, 
10% placebo) were the most common TEAEs following both active and placebo treatments. The 
incidence of treatment emergent AEs did not increase with rising GS-0976 dose levels. 
Most TEAEs in the study were of Grade 1 severity (39/41, 95 %) and were resolved by study 
completion. Three subjects experienced 4 TEAEs of Grade 2 severity including headache and 
nausea (placebo), arthralgia (GS-0976 20 mg), and dyspepsia (GS-0976 20 mg). No deaths or 
SAEs were reported. 
Overall, no clinically important trends in changes over time were noted in the laboratory results 
for GS-0976 active groups compared to placebo. 
1.3.
Rationale for the Current Study
Current evidence suggests that NASH is a consequence of the metabolic syndrome and 
lipotoxicity in the steatotic liver, which sets off an inflammatory response with subsequent 
activation of hepatic stellate cells and fibrogenesis. A key finding in patients with NASH is 
upregulation of the hepatic synthesis of fatty acids and triglycerides, referred to as de novo 
lipogenesis (DNL). Enhanced DNL in NASH occurs despite the excessive delivery of fatty acids 
to the liver from the diet as chylomicrons and from adipose tissue via lipolysis {Lambert 2014}.
DNL-derived fatty acids and their byproducts (e.g. diacylglycerol, lysophosphatidic acid, and 
eicosanoids) represent important signaling mediators that drive the lipotoxicity and inflammation 
characteristic of NASH {Neuschwander-Tetri 2010}. The first and rate-limiting step in DNL is 
the conversion of acetyl-coA to malonyl-coA by acetyl-coA carboxylase (ACC). ACC exists as 
two isoforms (ACC1 and ACC2). Whereas ACC1 is a cytosolic enzyme present in lipogenic 
tissues (e.g. liver and adipose), ACC2 is a mitochondria-associated enzyme present in oxidative 
tissues (e.g. liver, heart, and skeletal muscle) {Bianchi 1990, Kim 1997}. Inhibition of ACC1 
reduces DNL in lipogenic tissues while inhibition of ACC2 in oxidative tissues enhances 

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mitochondrial fatty acid oxidation {Harwood 2005}. Due to this unique position in intermediary 
metabolism {Harwood 2005, Tong 2006}, pharmacologic inhibition of ACC is an attractive 
strategy for limiting fatty acid synthesis while simultaneously stimulating fatty acid oxidation.
GS-0976 is a highly potent and selective allosteric inhibitor of ACC1 and ACC2. 
Pharmacodynamic studies indicate that GS-0976 reduces DNL, hepatic steatosis, inflammatory 
mediators, and fibrosis in preclinical models of liver disease {Harriman 2016}. In addition,
GS-0976 improves metabolic parameters (e.g. plasma triglycerides and free fatty acids, insulin, 
and leptin sensitivity) in high fat and high sucrose diet-induced obesity models. In total, these 
studies confirm the potential for GS-0976 to impact important histologic endpoints in NASH and 
also ameliorate the metabolic dysfunction frequently observed in these patients. Moreover, the 
liver-directed biodistribution of GS-0976 ensures that pharmacological effects are focused on the 
key target tissue for NASH and is anticipated to minimize effects outside of the liver.
In summary, the totality of the preclinical and clinical evidence, in addition to the large unmet 
medical need and the lack of existing therapies, suggests that the evaluation of GS-0976 in 
subjects with NASH, as proposed in the current study, is of merit.
1.3.1.
Rationale for this Study
This Phase 2 study has been designed as a multicenter, randomized, double-blind, 
placebo-controlled study evaluating the safety and efficacy of GS-0976 for 12 weeks in subjects 
with NASH. Approximately 125 NASH subjects without cirrhosis will be randomized in a 
2:2:1 ratio to receive GS-0976 at a dose of 5 mg or 20 mg orally QD, or placebo. Randomization 
will be stratified by the presence or absence of diabetes mellitus, a common comorbidity in 
patients with this condition. 
Inclusion criteria for the study were developed in order to noninvasively identify subjects with 
NASH. Specifically, all subjects will have a clinical diagnosis of NAFLD and evidence of
NASH histologically or based on magnetic resonance imaging; specifically, ≥8% hepatic 
steatosis on MRI-PDFF {Bannas 2015} and increased liver stiffness on MRE (≥2.5 kPa) {Park 
2016}. Previous studies have shown that patients with NAFLD and increased liver stiffness by 
MRE have a high probability of NASH on liver biopsy. For example, Park et al. reported that an 
MRE liver stiffness cut-off of ≥ 2.53 kPa was 64% sensitive, 68% specific, and had an area 
under the receiver operating characteristic curve (AUROC) of 0.70 and positive predictive value 
of 87% for the differentiation of simple steatosis from NASH on biopsy. Moreover, in this cohort 
of 104 patients, Park et al. demonstrated that a liver stiffness by MRE ≥2.65 kPa optimally 
identified the presence of at least stage 1 fibrosis (AUROC 0.82). Based on these criteria, 
subjects enrolled in this study have a high probability of NASH with fibrosis, a population with a 
large unmet medical need {Loomba 2014}. Since the safety and PK of GS-0976 have not yet 
been explored in subjects with cirrhosis, criteria have been developed in order to exclude 
cirrhotic subjects based on a validated serum marker for fibrosis (FibroTest®) and historical 
clinical, histological, and imaging data {Ratziu 2006}.
The primary endpoint of this study will be the safety and tolerability of GS-0976. In addition, the 
biological activity of GS-0976 will be determined based on endpoints including routine liver 

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biochemistry (e.g. ALT and GGT); noninvasive serum markers of liver injury (e.g. serum 
CK-18, FibroTest® and ELF™ Test); and imaging-based methods for quantifying hepatic 
steatosis (MRI-PDFF) and fibrosis (MRE and FibroScan®). An important endpoint of interest is 
the proportion of subjects achieving ≥ 30% reduction in steatosis as assessed by MRI-PDFF. 
This level of reduction has been associated with a significant improvement in NASH histology 
(≥ 2-point reduction in NAFLD Activity Score) {Patel 2015}. Based on preclinical and clinical
data, a treatment duration of 12 weeks with GS-0976 is expected to be sufficient to lead to 
meaningful improvements in hepatic steatosis on MRI-PDFF and liver biochemistry. Liver 
histology has not been included as an endpoint because it is not feasible to repeat this invasive 
procedure over a 12-week study. In addition to these liver-related endpoints, the effects of 
GS-0976 on carbohydrate and lipid metabolism (e.g. with glucose, insulin, free fatty acids, 
apolipoproteins, lipid profiles, and metabolites) will be closely monitored in light of the 
mechanism of action of GS-0976 and the importance of metabolic dysfunction in contributing to 
the morbidity and mortality (e.g. cardiovascular) of subjects with NASH.
The doses of GS-0976 chosen for evaluation in this study, 5 and 20 mg QD for 12 weeks, are 
supported by the safety, tolerability and effects of GS-0976 on DNL from studies 0976-101, 
0976-102, and 0976-103. As described in Section 1.2.5, single doses of GS-0976 up to 1000 mg 
or multiple daily doses (10 days) up to 200 mg were administered safely to healthy subjects in 
these studies. Moreover, a single dose of 20 mg resulted in a mean inhibition of fractional DNL 
of 71%. This level of DNL is postulated to be sufficient to achieve meaningful reductions in 
hepatic steatosis and lipid-derived inflammatory mediators that contribute to the pathogenesis of 
NASH. The four-fold GS-0976 dose range in this study will assess the impact of a range of 
GS-0976 systemic exposure on safety and effect of GS-0976 in subjects with NASH. 
Additionally, nonclinical toxicology studies up to 13 weeks in duration have been conducted in 
rats and dogs at exposure margins multiple folds above the expected clinical exposure. Based on 
preliminary data from studies 0976-101 (Section 1.2.5.1) and 0976-102 (Section 1.2.5.2), 
GS-0976 exposures in this study are expected to remain > 15 to 23-fold lower than the GS-0976 
exposures observed at the NOAELs in the 13-week rat and dog studies, respectively.
1.4.
Risk/Benefit Assessment for the Study
This study will provide information on the safety and efficacy of GS-0976 for the treatment of 
patients with NASH. As there are currently no approved therapies for NASH, there is a large 
unmet medical need for this growing population of patients. 
The potential benefits of GS-0976 for the treatment of NASH in the current study population 
include hypothesized improvements in hepatic steatosis and inflammation due to reduced DNL 
and increased beta oxidation that have been observed in pre-clinical and/or clinical studies of 
ACC inhibition. Improvements in liver biochemistry and hepatic fibrogenesis would be expected 
to ensue based on these effects.
To date, 96 subjects have received GS-0976 in Phase 1 studies in single doses up to 1000 mg or 
multiple daily doses (10 days) up to 200 mg. In general, treatment emergent adverse events 
(TEAEs) were mild to moderate with the predominant toxicities being gastrointestinal 

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(e.g. nausea, flatulence, diarrhea, constipation) in nature (see Section 1.2.5). Asymptomatic, 
Grade 3 or 4 elevations in blood triglycerides have been noted in 6 subjects treated for 10 days 
with GS-0976 at daily doses of 100 mg or higher. There is a potential risk to study participants of 
experiencing these and previously undetected side effects with longer term GS-0976 dosing. 
However, lower doses of 5 mg and 20 mg daily have been chosen for this study in order to 
mitigate this potential risk. Additional risks to study subjects include those attributable to study 
participation in general, including risks associated with frequent clinic visits and laboratory 
blood draws, and the associated pain and discomfort of phlebotomy. Strategies to mitigate these 
risks include close monitoring of lab values as well as AEs. Parameters for discontinuation of the 
study drugs due to AEs and laboratory abnormalities will be well-defined and closely followed.
In summary, there are no approved treatment options available for patients with NASH. Based 
on past clinical experience with GS-0976, the risk/benefit is positive and supports the continued 
evaluation of GS-0976 in this patient population. Data from this study will support the 
development of GS-0976 for the treatment of this condition.
1.5.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.

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2.
OBJECTIVES
The primary objective of this study is as follows:

To evaluate the safety and tolerability of GS-0976 in subjects with NASH.
The exploratory objectives of this study are as follows: 
CCI

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3.
STUDY DESIGN
3.1.
Study Design
This is a Phase 2, randomized, double-blind, placebo-controlled study designed to evaluate the 
safety, tolerability, and efficacy of GS-0976 in subjects with NASH. To be eligible to participate, 
subjects must have evidence of hepatic steatosis and increased liver stiffness as assessed by 
MRI-PDFF and MRE, respectively, or a historical liver biopsy consistent with NASH and non-
cirrhotic fibrosis. Any subject with history of decompensated liver disease, including ascites, 
hepatic encephalopathy or variceal bleeding will be ineligible.
The overall study design is presented graphically in Figure 3-1.
Figure 3-1.
Overall Study Design
3.2.
Treatment Plan and Regimen
Subjects meeting the study’s entry criteria will be randomly assigned in a 2:2:1 ratio to 1 of 3 
different treatment groups, A, B, and C, as shown in Figure 3-1. Randomization will be stratified 
by the presence or absence of diabetes mellitus as determined by medical history, use of 
medication for indication of diabetes mellitus, or based on Screening lab values if previously 
undiagnosed (i.e., hemoglobin A1c ≥ 6.5% OR fasting plasma glucose ≥126 mg/dL).
Study drugs will be administered for a total of 12 weeks from the Baseline/Day 1 visit. Dosage 
and administration of the study drugs and reference product are described in Section 5.3.
Group A (n=S0) 
GS-0976 5 mg+ 5 mg-PTM + 2 x 10 mg-PTM 
orally once daily 
C 
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bO 
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1ii 
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C 
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a, 
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2 x GS-0976 10 mg+ 2 x 5 mg-PTM 
a, 
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u 
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orally once daily 
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3.3. 
3.3.1. 
Bio marker Testing 
Biomarker Samples to Address the Study Objectives 
Final 
Amendment 1 
Biological specimens will be collected in this study as per the study procedures table to evaluate 
the association of explorato1y systemic and/or tissue specific biomarkers with study drugs 
response, pathway markers, including efficacy and/or adverse events and to increase knowledge 
and understanding of the biology of NASH or related diseases such as liver fibrosis, and 
inflammato1y diseases and/or the validation of a companion diagnostic for GS-0976 based upon 
the cunent state of scientific knowledge. Because biomarker science is a rapidly evolving area of 
investigation, it is not possible to specify prospectively all tests that will be done on the 
specimens provided. 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 aii knowledge. Samples 
will be will be stored for up to 15 years after the end of study. 
3.3.2. 
Biomarker Samples for Optional Future Research 
3.3.3. 
Biomarker Samples for Optional Genomic Research 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
This study will enroll approximately 125 subjects with NASH.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) Males and females between 18-75 years of age; inclusive based on the date of the Screening 
visit;
2) Willing and able to give informed consent prior to any study specific procedures being 
performed;
3) Meets the following conditions:
a) A clinical diagnosis of NAFLD with imaging or a liver biopsy documenting fatty liver 
within two years prior to Screening (if necessary, an ultrasound may be performed during 
Screening to confirm NAFLD), and 
b) Screening MRI-PDFF with ≥8% steatosis, and
c) Screening MRE with liver stiffness ≥ 2.5 kPa.  
Note: criterion 3a. must be met before evaluating criteria 3b. and 3c.
OR
d) A historical liver biopsy within 12 months of Screening consistent with NASH (defined 
as the presence of steatosis, lobular inflammation, and hepatocellular ballooning) with 
fibrosis, but not cirrhosis, and
e) No documented weight loss > 5% between the date of the liver biopsy and Screening.
4) Platelet count ≥ 100,000/mm3
5) Creatinine Clearance (CLcr ) as calculated by the Cockcroft-Gault equation ≥60 ml/min
6) Female subjects of childbearing potential (see definition in Appendix 3) must have a negative 
serum pregnancy test prior to starting study treatment;
7) All female subjects of childbearing potential who engage in heterosexual intercourse must 
agree to use a highly effective method of contraception during intercourse from the 
Screening visit throughout the study period and for 30 days following the last dose of study 
drugs (see Appendix 3 for details);

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8) Male subjects are required to use barrier contraception (condom plus spermicide) during 
intercourse from the Screening through the study completion and for 90 days following the 
last dose of study drugs (see Appendix 3 for details); 
9) Male subjects must refrain from sperm donation from Screening through at least 90 days 
following the last dose of study drugs.
10) Female subjects must refrain from egg donation or harvest for 30 days after last dose of study 
drugs.
11) Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, 
other study procedures, and study restrictions.
12) Must be able to read and complete Quality of Life questionnaires independently.
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria will not be randomized in this study.
1) Pregnant or lactating females; lactating females must agree to discontinue nursing before the 
study drugs are administered;
2) ALT > 5 x ULN;
3) Other causes of liver disease including autoimmune, viral, and alcoholic liver disease;
4) Cirrhosis of the liver as defined by any of the following:
a) Cirrhosis on historical liver biopsy (e.g. NASH CRN classification stage 4 or equivalent);
b) Evidence of cirrhosis on liver imaging (e.g. ultrasound, CT, or MRI) including a nodular 
liver surface, splenomegaly, or portal venous collaterals;
c) Prior history of decompensated liver disease, including ascites, hepatic encephalopathy or 
variceal bleeding;
d) Screening FibroSURE/FibroTest® ≥ 0.75, unless a historical liver biopsy within 
12 months of Screening does not reveal cirrhosis. In patients with Gilbert’s syndrome or 
hemolysis, FibroSURE/FibroTest® will be calculated using direct bilirubin instead of 
total bilirubin.
5) History of liver transplantation;
6) Weight reduction surgery in the 2 years prior to Screening or planned during the study 
(weight reduction surgery is disallowed during the study);
7) History of intestinal resection or malabsorptive condition that may limit the absorption of 
GS-0976. Prior cholecystectomy and appendectomy are permitted

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8) BMI < 18 kg/m2;
9) INR > 1.2, unless on anticoagulant therapy;
10) Total bilirubin > 1 x ULN, except with diagnosis of Gilbert’s syndrome;
11) Chronic hepatitis B (HBsAg positive);
12) Chronic hepatitis C (HCV Ab and HCV RNA positive). Subjects cured of HCV infection less 
than 2 years prior to the Screening visit are not eligible.
13) HIV Ab positive;
14) Alcohol consumption greater than 21 oz/week for males or 14 oz/week for females 
(1oz/30mL of alcohol is present in 1 12oz/360mL beer, 1 4oz/120mL glass of wine, and a 
1 oz/30 mL measure of 40% proof alcohol);
15) Positive urine screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at 
Screening. Subjects on stable methadone or buprenorphine maintenance treatment for at least 
6 months prior to Screening may be included in the study. Subjects with a positive urine drug 
screen due to prescription opioid-based medication are eligible if the prescription and 
diagnosis are reviewed and approved by the investigator;
16) Unstable cardiovascular disease as defined by any of the following:
a) Unstable angina within 6 months prior to Screening
b) Myocardial infarction, coronary artery bypass graft surgery or coronary angioplasty 
within 6 months prior to Screening
c) Transient ischemic attack or cerebrovascular accident within 6 months prior to Screening
d) Obstructive valvular heart disease or hypertrophic cardiomyopathy
e) Congestive heart failure;
17) Use of prohibited concomitant medications as described in Section 5.4
18) History of a malignancy within 5 years prior to Screening with the following exceptions:
a) Adequately treated carcinoma in situ of the cervix
b) Adequately treated basal or squamous cell cancer or other localized non-melanoma skin 
cancer;
19) Any laboratory abnormality or condition that, in the investigator’s opinion, could adversely 
affect the safety of the subject or impair the assessment of study results;
20) Participation in another investigational study of a drug or device within 28 days prior or 
within 5 half-lives of the prior investigational agent (whichever is longer) prior to Screening;
21) Concurrent participation in another therapeutic clinical study;

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22) Known hypersensitivity to GS-0976, the metabolites, or formulation excipient;
23) Presence of any condition that could, in the opinion of the investigator, compromise the 
subject’s ability to participate in the study, such as history of substance abuse or a psychiatric 
(including any subjects with a psychiatric hospital admission or emergency room visit in the 
2 years prior to Screening) or medical condition;
24) Unavailable for follow-up assessment or concern for subject’s compliance with the protocol 
procedures;
25) Contraindications or inability to complete MRI scanning (e.g. presence of permanent 
pacemakers, implanted cardiac devices, weight restrictions, etc.).
Subjects with laboratory abnormalities outside of the above parameters may be approved for 
inclusion in the trial with approval from the Medical Monitor.

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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
This is a randomized, double-blind, placebo-controlled study. Subjects meeting the study entry 
criteria will be randomly assigned in a 2:2:1 ratio to 1 of 3 different treatment group as described 
in Section 5.3.
5.1.
Randomization, Blinding and Treatment Codes
An Interactive Web Response System (IWRS) will be used for centralized randomization and 
treatment assignment. Randomization will be stratified by the presence or absence of diabetes 
mellitus as determined by medical history, use of medication for indication of diabetes mellitus, 
or based on Screening lab values if previously undiagnosed (ie, hemoglobin A1c ≥ 6.5% OR 
fasting plasma glucose ≥126 mg/dL).
Investigative site personnel will obtain the subject’s identification number and study drug 
assignment from the IWRS. Subjects and all personnel directly involved in the conduct of the 
study will be blinded to treatment assignment.
Study drugs will be dispensed by the study pharmacist, or designee, in a blinded fashion to the 
subjects.
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 (or designee)  may obtain treatment assignment directly from the 
IWRS system for that subject (refer to Study Reference Binder for IWRS unblinding
instructions). Gilead recommends but does not require that the investigator contact the Gilead 
medical monitor before breaking the blind. Treatment assignment should remain blinded unless 
that knowledge is necessary to determine subject emergency medical care. The rationale for 
unblinding must be clearly explained in source documentation and on the electronic case report 
form (eCRF), along with the date on which the treatment assignment was obtained. The 
investigator is requested to contact the Gilead medical monitor promptly in case of any treatment 
unblinding.
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a 
subject’s treatment assignment is disclosed to the investigator, the subject will have study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject.
Gilead Drug Safety and Public Health (DSPH) may independently unblind cases for expedited 
reporting of suspected unexpected serious adverse reactions (SUSARs).

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5.2.
Description and Handling of Study Drugs
5.2.1.
Formulation
GS-0976 will be supplied as white opaque size 0 hard gelatin capsules containing 10 mg of 
GS-0976, and as white opaque size 2 hard gelatin capsules containing 5 mg of GS-0976. In 
addition to the active ingredient, GS-0976 capsules contain the following inactive ingredients: 
lactose monohydrate, stearoyl polyoxylglycerides and croscarmellose sodium, which are 
common pharmaceutical excipients.
Placebo-to-match (10 mg-PTM and 5 mg-PTM) GS-0976 capsules are identical in size, shape, 
color and appearance to their corresponding strengths of active GS-0976 capsules. PTM 
GS-0976 capsules contain lactose monohydrate.
5.2.2.
Packaging and Labeling
GS-0976 capsules and PTM GS-0976 are packaged in white, high density polyethylene (HDPE) 
bottles. Each bottle contains 30 capsules.  Each bottle is enclosed with a white, continuous 
thread, child-resistant polypropylene screw cap with an induction-sealed and aluminum-faced 
liner.
Study drugs to be distributed to centers in the US shall be labeled to meet applicable 
requirements of the United States Food and Drug Administration (FDA) and/or other local 
regulations.
5.2.3.
Storage and Handling
GS-0976 and PTM GS-0976 should be stored at controlled room temperature of 25 °C (77 °F); 
excursions are permitted between 15°C and 30°C (59°F and 86°F).  Storage conditions are 
specified on the label.  Until dispensed to the subjects, all bottles of study drugs should be stored 
in a securely locked area, accessible only to authorized site personnel. 
To ensure the stability and proper identification, study drugs should not be stored in a container 
other than the container in which they were supplied. 
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure when handling.
5.3.
Dosage and Administration of GS-0976/PTM GS-0976 
GS-0976 capsules will be provided by Gilead Sciences.  Subjects will take 4 capsules of 
GS-0976 (5 mg, 5 mg-PTM, 10 mg, or 10 mg-PTM) once daily at approximately the same time 
each morning.  Study drugs should be swallowed whole with water and may be taken with or 
without food.  A dose will be considered missed if the subject cannot take the dose within 
12 hours of their regular dosing time.  If a subject misses a dose, the subject should take their 

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next dose at the regular dosing time. Study drug dosing and administration will occur as follows, 
based on treatment group randomization:

Treatment Group A: GS-0976 5 mg (1 x 5 mg capsule + 1 x 5 mg-PTM 
capsule + 2 x 10 mg-PTM capsules) administered orally once daily;

Treatment Group B: GS-0976 20 mg (2 x 10 mg capsules + 2 x 5 mg-PTM capsules) 
administered orally once daily;

Treatment Group C: GS-0976 Placebo (2 x 5 mg-PTM capsules + 2 x 10 mg-PTM capsules) 
administered orally once daily.
5.4.
Prior and Concomitant Medications
All concomitant medication will be recorded in the source documents and eCRFs.  This includes 
concomitant medications taken within 30 days prior to Screening and any taken during the study 
to the end of the follow-up period.
The following medications are prohibited from 28 days prior to Baseline/Day 1 up to and 
including the day of the last dose of study drugs:

Hematologic stimulating agents (e.g. erythropoiesis-stimulating agents (ESAs); granulocyte 
colony stimulating factor (GCSF); thrombopoietin (TPO) mimetics)

Chronic systemic immunosuppressants including, but not limited to, corticosteroids 
(prednisone equivalent of > 10 mg/day for > 2 weeks), azathioprine, or monoclonal 
antibodies (eg, infliximab). Use for ≤ 2 weeks total is allowed.

Investigational agents or devices for any indication

Concomitant use of certain medications or herbal/natural supplements (inhibitors or inducers 
of drug transporters P-gp, or OATP1B3 or 1B3, or substrates of CYP3A which are sensitive 
to induction) with GS-0976 may result in PK interactions resulting in increases or decreases 
in exposure of GS-0976 or concomitant medications. Examples of representative medications 
which are prohibited from 28 days prior to Baseline/Day 1 through the treatment period are 
listed below in Table 5-1:

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Table 5-1.
List of Prohibited Medications
Drug Class
Agents Disallowed
Antibiotics
Azithromycin, Clarithromycin, Erythromycin
Anticonvulsantsa
Phenobarbital, Phenytoin, Carbamazepine, Oxcarbazepine
Antifungals
Itraconazole, Ketoconazole
Antimycobacterialsa
Rifamycins, Isoniazid
Cardiac Medications
Amiodarone, Digoxin, Dronedarone, Felodipine, Verapamil, 
Quinidine, Ranolazine, Bosentan, Olmesartan, Telmisartan, 
Valsartan
Herbal/Natural Supplementsa
St. John’s Wort, Echinaccea. Milk thistle (i.e. silymarin), Chinese 
herb sho-saiko-to (or Xiao-Shai-Hu-Tang)
Selective Serotonin Reuptake Inhibitors
Fluvoxamine
Other
Gemfibrozil, Modafinil
a
May result in a decrease in the concentrations of study drugs.
Medications for disease conditions excluded from the protocol (e.g., HIV-1, HBV, or HCV
infection, active cancer, transplantation) are not listed under this Concomitant Medication 
section and are disallowed in the study.
5.5.
Accountability for GS-0976/PTM GS-0976
The investigator or designee (e.g., pharmacist) is responsible for ensuring adequate 
accountability of all used and unused study drug bottles. This includes acknowledgement of 
receipt of each shipment of study drug (quantity and condition), subject dispensing records, and 
returned or destroyed study product. All used and unused study drug bottles 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 bottles

Record the date, subject number, subject initials, and the study drug bottle number dispensed

Record the date, quantity of used and unused study drug returned, along with the initials of 
the person recording the information.
5.5.1.
Investigational Medicinal Product Return or Disposal
Refer to Section 9.1.7 for instructions regarding study drug return or disposal.

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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject randomized in the study are presented in 
tabular form in Appendix 2 and described in the text that follows. Additional information is 
provided in the Study Reference Binder.
The investigator must document any deviation from protocol procedures and notify the Sponsor 
or the Contract Research Organization (CRO).  
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the investigator to ensure that subjects are eligible to participate in the 
study prior to enrollment and throughout the study. 
Documentation of the personally signed and dated informed consent of each subject, using the 
study-specific ICF, is required before initiating the Screening process.
After written informed consent has been obtained and eligibility to participate established, 
investigative site personnel will obtain the subject’s identification number and study drug 
assignment from the interactive web response system (IWRS).
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 6 weeks prior to randomization to determine eligibility for 
participation in the study. The Screening period may be extended under special circumstances 
with the explicit approval of the Gilead Medical Monitor.
Subjects who previously failed screening in GS-US-426-3989 can be re-screened in the 
following situations:

Previously screen failed due to a low MRE or MRI-PDFF measurement, but have an 
MRE ≥2.5 kPa and MRI-PDFF ≥8% within 6 months of prior Screening/Re-screening.

Previously screen failed due to a low MRE or MRI-PDFF measurement and have a historical 
liver biopsy within 12 months of Screening/Re-screening that is consistent with NASH 
(defined as the presence of steatosis, hepatocellular ballooning, and lobular inflammation) 
with fibrosis, but not cirrhosis. 

Previously screen failed due to a FibroSURE/FibroTest® ≥ 0.75 in whom Gilbert’s syndrome 
or hemolysis is present; a repeat FibroSURE/FibroTest® calculated using direct bilirubin 
instead of total bilirubin will be used to determine eligibility. 

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
Previously screen failed due to a FibroSURE/FibroTest® ≥ 0.75 and with a historical liver 
biopsy within 12 months of Screening that does not reveal cirrhosis; FibroSure/Fibrotest 
score will not be used to determine eligibility.
If MRE and MRI-PDFF were performed within 6 months of re-screening, MRE and MRI-PDFF 
does not need to be repeated. If prior imaging was performed greater than 6 months prior to 
re-screening, MRE and MRI-PDFF must be repeated. A historical MRE and MRI-PDFF within 
6 months of screening in another Gilead study (i.e. GS-US-384-3914, GS-US-402-1852) may be 
used to determine eligibility into this study. All other screening procedures must be repeated and 
meet eligibility criteria.
Screening labs may be repeated within the Screening period, prior to administration of study 
drugs to rule out laboratory error, if any. This will be done at the discretion of the investigator.
Subjects should be instructed to fast (no food or drink, except water), starting from midnight 
(00:00) or earlier, as appropriate, on the evening prior to the Screening visit to ensure an 
approximate 8-hour fast prior to the fasted blood sample collection the next morning.
The following will be performed and documented at Screening:

Obtain written informed consent before initiation of any Screening procedures

Review and record whether the subject meets inclusion and exclusion criteria

Obtain Screening number from IWRS

Obtain medical history

Complete physical examination

Record vital signs, body weight, and height

Obtain blood samples for:
Chemistry
Hematology 
Coagulation Panel 
Hemoglobin A1c
HIV-1, HBV and HCV serology (if HCV Ab positive, reflex to HCV RNA.)
Serum pregnancy test (only for female subjects of child bearing potential - see
Appendix 3.)

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• 
Conduct standard 12-Lead ECG 
• 
Perfo1m ultrasound (if necessaiy) for confnmation of NAFLD 
• 
Perfo1m MRE and MRI-PDFF 
• 
Review any historical liver biopsy results, if available. 
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• 
Urine diug screen for amphetamines, cocaine and opiates (i.e., heroin, morphine) 
• 
Record all concomitant medications that the subject has taken within 30 days prior to 
Screening 
• 
Record any serious adverse events and all adverse events related to protocol mandated 
procedures occuning after signing of the consent fo1m . 
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 6 weeks of the staii of Screening for randomization into the study. The screening 
period may be extended under special circumstances with the explicit approval of the Medical 
Monitor. 
From the time of obtaining infonned consent through the first adininistration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events electronic case repo1i fonn 
(eCRF). All other untoward medical occmTences observed during the Screening period, 
including exacerbation or changes in medical histo1y are to be captured on the medical histo1y 
eCRF. See Section 7 Adverse Events and Toxicity Management for additional details. 
6.3. 
Baseline/Day 1 Randomization and Assessments 
Subjects retmning to the clinic for randomization at Baseline/Day 1 should be instructed to fast 
(no food or di·ink, except water), staiiing from midnight (00:00) or eai·lier, as appropriate, on the 
evening prior to the Baseline/Day 1 visit to ensure an approximate 8-hour fast prior to the blood 
sainple collection under fasting conditions the next morning. 
After review of inclusion and exclusion criteria to confnm continued eligibility, subjects will be 
randomized to study diug assignment and receive their Subject Identification Number via the 
IWRS prior to their first dose of study mugs. 
Randomization will be sti·atified by the presence or absence of diabetes mellitus as detennined 
by medical histo1y, use of medication for indication of diabetes mellitus, or based on Screening 
lab values if previously undiagnosed (ie, hemoglobin Ale~ 6.5% OR fasting plasma 
glucose~ 126 mg/dL). 
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The following will be perfonned and documented at the Baseline/Day 1 visit prior to dosing: 
• 
QoL Questionnaires (SF-36, WPAI, and CLDQ) 
Note: It is recommended that QoL questionnaires be completed prior to any study procedures 
being perfo1med and prior to the subject seeing a health care provider. 
• 
Symptom driven physical examination 
• 
Record vital signs, waist circmnf erence, and body weight 
• 
Obtain blood samples for: 
-
Chemistiy 
-
Hematology 
-
Coagulation Panel 
-
Lipid Profile 
-
Hemoglobin Ale 
-
Biomarkers 
• 
Conduct standard 12-Lead ECG 
• 
Perfo1m FibroScan® (if available) 
• 
Collect urine samples for: 
-
Urine pregnancy test for females of child bearing potential only 
-
Biomarkers 
• 
Collect stool sample for Biomarkers (see Study Reference Binder for instiuctions) 
• 
Dispense study mugs, and provide subject with insti11ction on appropriate dosing and 
adininisti·ation; subject will take the Baseline/Day 1 dose of study di11gs on-site 
• 
Record all concomitant medications that the subject has taken since the previous visit 
• 
Record any serious adverse events and all adverse events occuning since the Screening visit 
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Subjects will return to the investigative site at Week 1 (±3 days) for a mandatory safety visit. 
Then, starting at the Week 4 visit, subjects will have visits every 4 weeks up to the Week 12
visit.
6.4.
Treatment Assessments
6.4.1.
Week 1 Visit (±3 days)
Subjects should be instructed to fast (no food or drink, except water), starting from midnight 
(00:00) or earlier, as appropriate, on the evening prior to the Week 1 visit to ensure an 
approximate 8-hour fast prior to the fasted blood sample collection the next morning.
Subjects should also be instructed to HOLD their dose of study drugs on the day of their Week 1 
visit until all visit procedures have been completed. The study drugs should be taken after the 
visit.
During the Week 1 safety visit (±3 days), the subject will return to the investigative site and the 
following will be performed and documented:

Symptom driven physical examination

Record vital signs, and body weight

Obtain blood samples for:
Chemistry
Hematology
Coagulation Panel
Lipid Profile
Biomarkers
Single PK sampling

Collect urine sample for biomarkers

Record all concomitant medications that the subject has taken since the previous visit

Record any serious adverse events and all adverse events occurring since the previous visit

Review of study drug dosing compliance (pill count)

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6.4.2.
Week 4 Visit (±3 days)
Subjects should be instructed to fast (no food or drink, except water), starting from midnight 
(00:00) or earlier, as appropriate, on the evening prior to the Week 4 visit to ensure an 
approximate 8-hour fast prior to the fasted blood sample collection the next morning.
Subjects should also be instructed to HOLD their dose of study drugs on the day of their Week 4 
visit until all visit procedures have been completed. The study drugs should be taken after the 
visit.
The following will be performed and documented at this visit (±3 days):

Symptom driven physical examination

Record vital signs, and body weight

Obtain blood samples for:
Chemistry
Hematology
Coagulation Panel
Lipid Profile
Biomarkers
Single PK sampling

Collect urine samples for:
Urine pregnancy test for females of child bearing potential only
Biomarkers

Dispense study drugs

Record all concomitant medications that the subject has taken since the previous visit

Record any serious adverse events and all adverse events occurring since the previous visit

Review of study drug dosing compliance (pill count)
6.4.3.
Week 8 Visit (±3 days)
Subjects should be instructed to fast (no food or drink, except water), starting from midnight 
(00:00) or earlier, as appropriate, on the evening prior to the Week 8 visit to ensure an 
approximate 8-hour fast prior to the fasted blood sample collection the next morning.

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Subjects should also be instructed to HOLD their dose of study drugs on the day of their Week 8 
visit until all visit procedures have been completed. The study drugs should be taken after the 
visit.
The following will be performed and documented at these visits (±3 days):

Symptom driven physical examination

Record vital signs, and body weight

Obtain blood samples for:
Chemistry
Hematology
Coagulation Panel
Lipid Profile
Single PK sampling

Urine pregnancy test for females of child bearing potential only

Dispense study drugs

Record all concomitant medications that the subject has taken since the previous visit

Record any serious adverse events and all adverse events occurring since the previous visit

Review of study drug dosing compliance (pill count)
6.4.4.
Week 12 Visit (±7 days)
Subjects should be instructed to fast (no food or drink, except water), starting from midnight 
(00:00) or earlier, as appropriate, on the evening prior to the Week 12 visit to ensure an 
approximate 8-hour fast prior to the fasted blood sample collection the next morning.
Subjects should also be instructed to HOLD their dose of study drugs on the day of their 
Week 12 visit until all visit procedures have been completed. The study drugs should be taken 
after the visit.
The following will be performed and documented at this visit (±7 days):

QoL Questionnaires (SF-36, WPAI, and CLDQ)

Symptom driven physical examination

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
Record vital signs, waist circumference, and body weight

Obtain blood samples for:
Chemistry
Hematology
Coagulation Panel
Lipid Profile
Hemoglobin A1c
Biomarker
Single PK sampling

Collect urine samples for:
Urine pregnancy test for females of child bearing potential only
Biomarkers

Conduct standard 12-Lead ECG

Perform FibroScan® (if available)

Perform MRE and MRI-PDFF

Collect stool sample for Biomarkers (see Study Reference Binder for instructions)

Record all concomitant medications that the subject has taken since the previous visit

Record any serious adverse events and all adverse events occurring since the previous visit

Review of study drug dosing compliance (pill count)
6.4.5.
Unscheduled Visit
Additional unscheduled assessments may be performed at the discretion of the investigator.
Subjects returning to the clinic for an unscheduled visit should be instructed to fast (no food or 
drink, except water), starting from midnight (00:00) or earlier, as appropriate, on the evening 
prior to the visit to ensure an approximate 8-hour fast prior to the blood sample collection under 
fasting condition the next morning.

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Subjects should also be instructed to HOLD their dose of study drugs on the day of an 
unscheduled visit until all visit procedures have been completed. The study drugs should be 
taken after the visit.
At a minimum, the following will be performed and documented.

Symptom driven physical examination

Obtain blood samples for:
Chemistry
Hematology

Record body weight

Record all concomitant mediations that the subject has taken since the previous visit

Record any serious adverse events and all adverse events occurring since the previous visit
If the Unscheduled visit is performed for the sole purpose of distribution of study drug, the 
assessments noted above do not need to be performed.
6.4.6.
Follow-Up Visit (±5 days)
Subjects will return for a Follow-Up visit, four weeks after the date of last dose of study drugs.
Subjects should be instructed to fast (no food or drink, except water), starting from midnight 
(00:00) or earlier, as appropriate, on the evening prior to the Follow-up visit to ensure an 
approximate 8-hour fast prior to the blood sample collection under fasting condition the next 
morning.
The following will be performed and documented at this visit (±5 days):

Symptom driven physical examination

Record vital signs, and body weight

Obtain blood samples for:
Chemistry
Hematology
Coagulation Panel
Lipid Profile

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• 
Record all concomitant medications that the subject has taken since the previous visit 
• 
Record any serious adverse events and all adverse occmTing since the previous visit 
6.5. 
Assessments for Premature Discontinuation from Study 
Subjects prematmely discontinuing from the study (for example, as a result of an AE), should 
have an Early Tennination (ET) visit, if possible, and a Follow-Up visit 4 weeks after the date of 
last dose of study dmgs. The study assessments to be perfo1med at the ET visit are the same as 
those perfonned at the Week 12 visit (refer to Section 6.4.4). The study assessments to be 
perfo1med at the Follow-Up visit are listed in Section 6.4.6. The subject will then be withdrawn 
from the study. 
If these visits are not possible or acceptable to the subject or investigator, the subject may be 
withdrawn from the study. 
6.6. 
Criteria for Discontinuation of Study Treatment 
Study medication may be discontinued in the following instances: 
• 
IntercmTent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercunent illness, the subject 
may resume study dosing at the discretion of the investigator. 
• 
Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedmes or is considered to not be in the subject's best 
interest 
• 
Subject request to discontinue for any reason 
• 
Subject noncompliance 
• 
Pregnancy dming the study; refer to Appendix 3. 
• 
Sponsor discretion 
• 
Discontinuation of the study at the request of Gilead, a regulato1y agency or an institutional 
review board or independent ethics committee (IRB/IEC) 
6.7. 
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6.8. 
Description of Assessments 
6.8.1. 
Clinical Laboratory Analytes 
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Fasting is required prior to all study visits. All study procedures will be perfo1med before dosing 
while the subject is in a fasted state. Subjects will take their dose of study diugs after the study 
visit has concluded. 
Chemistiy: 
Alanine aininoti·ansferase (ALT), aspartate aminotl'ansferase (AST), albumin, alkaline 
phosphatase (ALP), bicarbonate, blood urea niti·ogen (BUN), calcium, chloride, creatinine, 
glucose, lactate dehydi·ogenase (LDH), magnesium, phosphorns, potassium, sodium, total and 
direct bilirnbin, total protein, uric acid, gamma-glutamyl ti·ansferase (GGT). Also includes 
C-Peptide and Insulin for the Baseline/Day!, Week 4, and 12 visits. 
Creatinine clearance is calculated by the Cockcroft-Gault equation {Cockcroft 1976} using actual 
body weight (BW). The calculation will be perfonned by the centi·al laborato1y. 
Hematology: 
Hematocrit (Hct), Hemoglobin (Hb ), Platelet count, Red blood cell count (RBC), White blood 
cell count (WBC) with differential (absolute and percentage) including Lymphocytes, 
Monocytes, Neutl'ophils, Eosinophils, and Basophils and, Reticulocyte count and mean 
corpuscular volume (MCV). 
Coagulation Panel: 
INR, Prothrombin time (PT), paiiial thromboplastin time (PTT) 
Pregnancy Tests: 
Sernm P-hCG or urine P-hCG (if positive, requires immediate confomation with Sernm P-hCG) 
Additional Tests: 
Lipid Profile, Hemoglobin Ale, HIV-I, HBV & HCV Serology (ifHCV A~ 
s), sern1~ 
and genomic sample 
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Biomarkers: 
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fucluding but not limited to: CK18 (M30 and M65), FGF19, C4, Apolipoprotein B (Apo B), 
metabolite profile, bile acids, stool microbiome, blood miRNA, NMR lipoprofile, free fatty 
acids, ELF™ Test, and FibroSURE/FibroTest®. 
Phaimacokinetic (PK) Assessments: 
Single PK Sampling 
Single PK samples will be collected and ai·chived for PK analysis of GS-0976 and other 
metabolites as applicable 
6.8.2. 
Physical Examination 
A complete physical examination should include source documentation of general appearance, 
and the following body systems: head, neck, and thyroid; eyes, eai·s, nose, throat, mouth, and 
tongue; chest ( excluding breasts); respirato1y; cai·diovasculai·; lymph nodes; abdomen; skin, hair, 
nails; musculoskeletal; neurological. 
The focus of a symptom driven physical examination will be detennined by the investigator 
based on subject complaint. For example, if a subject complains of a cough, a lung exam should 
be perfonned. If consistent with pneumonia (rales/crackles on exam) then an AE would be 
documented. 
Height, body weight, and hip circumference will be collected at specified time points. 
6.8.3. 
Vital Signs 
Assessment of vital signs will include measurement of resting blood pressure, pulse, respirato1y 
rate and temperature. 
Blood pressure will be measured using the following standardized process: 
• 
Subject should sit for 
5 minutes with feet flat on the floor and measurement aim suppo1ied 
so that the midpoint of the manometer cuff is at heaii level; 
• 
Use a mercmy sphygmomanometer or automatic blood pressure device with an appropriately 
sized cuff with the bladder centered over the brachia! a1ie1y; 
Measure and record the blood pressure to the nearest 2 mmHg mark on the manometer or to the 
nearest whole number on an automatic device. 
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6.8.4.
Medical History
Medical history, including details regarding illnesses and allergies, date(s) of onset, and whether 
condition(s) is currently ongoing, and medication history will be collected on all subjects during 
Screening. If available, historical liver biopsy information will also be collected.
6.8.5.
Pharmacogenomic Testing
From subjects who agree to participate and provide consent, one blood sample will be obtained. 
This sample should be collected at the Day 1 visit, but may be collected at any time during the 
study or at a separate poststudy visit, if necessary. 
6.8.6.
Health Related Quality of Life (HRQoL)
It is recommended that these questionnaires be completed prior to the clinical and laboratory 
assessments. The subject should read the questionnaires by himself/herself and record the 
answers by himself/herself.
6.8.6.1.
SF-36 Health Survey
The SF-36 Health Survey asks 36 questions to measure functional health and well-being from the 
subject’s point of view and consists of eight health domains (physical functioning, role-physical, 
bodily pain, general health, vitality, social functioning, role-emotional, and mental health). These 
health domain scales contribute to the physical health and mental health summary measures.
6.8.6.2.
CLDQ
The CLDQ asks 29 questions related to liver disease to measure health related quality of life in 
subjects with chronic liver disease.
6.8.6.3.
WPAI
The Work Productivity and Activity Impairment (WPAI) questionnaire asks 6 questions 
regarding the effect of NASH on a person’s ability to work and perform regular activities. 
6.8.7.
Electrocardiogram
Standard 12-lead electrocardiogram (ECG) assessments will be performed. The Investigator will 
review the ECGs for any clinically significant abnormalities to ensure subject safety. Abnormal 
ECG findings that are considered clinically significant by the Investigator and meet the 
definition of an AE should be reported and recorded in the AE eCRF page.
6.8.8.
FibroScan®
The sites will perform liver stiffness assessments by FibroScan®. It is required that each subject 
have the FibroScan® assessments done with the same type of probe at Baseline Day 1 and 
Week 12 visits (if available).

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6.8.9.
MRE and MRI-PDFF
Liver stiffness will be assessed by MRE (shear wave 60 Hz) and the degree of steatosis will be 
measured by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF). These 
assessments can occur sequentially.
The MRE and MRI-PDFF images will be analyzed by a central reader. 
Please refer to the Study Reference Binder for MRE and MRI-PDFF imaging guidelines. 
6.9.
End of Study Definition
Subjects are considered to have completed the study after the completion of the Week 16 
Follow-Up visit, regardless of treatment duration or early termination of study drugs.
6.10.
Poststudy Care
No poststudy ongoing care will be provided.
6.11.
Sample Storage
Residual biological samples from all visits will be frozen and stored if specific consent is 
obtained. These stored samples may be used by Gilead or research partners of Gilead to help 
answer questions about the study drugs, NASH, and its associated conditions, or clinical 
laboratory testing to provide additional safety data. No human genetic testing will be performed 
without express consent of the study subjects. At the conclusion of this study, these samples may 
be retained in storage for Gilead for a period of up to 15 years.

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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 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 posttreatment complications that occur as a result of protocol 
specified procedures, 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 AE and must be reported.

Preexisting 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 7.6.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be preexisting and should be documented on the medical history 
eCRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization

Persistent or significant disability/incapacity

A congenital anomaly/birth defect

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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.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to study drug interruption, modification, 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 respectively.. If the 
laboratory abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not 
the laboratory result (ie, decreased hemoglobin).
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 study 
drugs using clinical judgment and the following considerations:

No: Evidence exists that the AE has an etiology other than the study drugs. For SAEs, an 
alternative causality must be provided (eg, preexisting condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the study drugs.
It should be emphasized that ineffective treatment should not be considered as causally related in 
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The relationship to study procedures (eg, invasive procedures such as venipuncture) should be 
assessed using the following considerations:

No: Evidence exists that the AE has an etiology other than the study procedure.

Yes: The AE occurred as a result of protocol procedures, (eg, venipuncture)
7.2.2.
Assessment of Severity
The severity grading of AEs will be assessed as Grade 1, 2, 3, 4, or 5 according 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
(see Appendix 4).
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events listed above.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (eCRF): all SAEs and AE related to 
protocol-mandated procedures.
7.3.1.1.
Adverse Events
Following initiation of study medication until 30 days after last administration of study drugs, all 
AEs, regardless of cause or relationship must be reported to the eCRF database as instructed.
All AEs should be followed up until resolution or until the AE is stable, if possible. 
Gilead Sciences, Inc. may request that certain AEs be followed beyond the protocol defined 
follow-up period.
7.3.1.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required posttreatment follow-up period, must be reported to the 
eCRF database and Gilead Drug Safety and Public Health (DSPH) as instructed. This also 
includes any SAEs resulting from protocol-associated procedures performed after ICF is signed.

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Any SAEs and deaths that occur after the posttr·eatment follow-up visit but within 30 days of the 
last dose of study diugs, regardless of causality, should also be repo1ied. 
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 di11gs, he/she should promptly document and 
repo1i the event to Gilead DSPH. 
• 
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline. 
7.3.1.3. 
Elech'onic Serious Adverse Event ( eSAE) Repo1i ing Process 
• 
Site personnel record all SAE data in the eCRF database and from there tr·ansmit the SAE 
infonnation to Gilead DSPH within 24 hours of the investigator's knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines. 
• If for any reason it is not possible to record the SAE infonnation elech'onically, i.e., the 
eCRF database is not functioning, record the SAE on the paper serious adverse event 
repo1i ing fo1m and submit within 24 hours to: 
Gilead DSPH Fax: IPIPD 
Email: IPIPD 
• 
As soon as it is possible to do so, any SAE reported via paper must be tr·anscribed into the 
eCRF Database according to instructions in the eCRF completion guidelines. 
• If an SAE has been repo1ied via a paper fonn because the eCRF database has been locked, no 
fuither action is necessaiy. 
• 
For fatal or life-threatening events, copies of hospital case repo1is, autopsy repo1is, 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 tr·aceability of a document to the subject identifiers. 
• 
Additional infonnation may be requested to ensure the timely completion of accurate safety 
repo1is. 
• 
Any medications necessaiy for tr·eatment of the SAE must be recorded onto the concomitant 
medication section of the subject's eCRF and the event description section of the SAE fonn. 
7.4. 
Gilead Reporting Requirements 
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the European Union (EU) Clinical Trials Directive (2001/20/EC) and 
relevant updates, and other country-specific legislation or regulations, Gilead may be required to 
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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 IB or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study drugs. 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.
Toxicity Management 
Observation for Drug Induced Liver Injury (DILI):
Although subjects randomized in this study will have baseline liver disease, their hepatic 
function should not be significantly impaired. However, at baseline, some may have liver 
biochemistry levels above the upper limit of normal (ULN). 
For subjects with ALT and AST below ULN at study start, close observation for DILI 
(as described below) should be considered in subjects with any of the following criteria (all labs 
confirmed by repeat testing):

ALT or AST > 3 x ULN at any time

Total bilirubin > 2 x ULN

ALP > 3 x ULN

INR >1.5 x ULN (except for subjects on anticoagulant therapy)  

Clinical signs or symptoms that are, in the opinion of the investigator, consistent with 
hepatitis (such as right upper quadrant discomfort, fever, nausea, vomiting, jaundice, rash, or 
eosinophilia > 5%)
For subjects with ALT or AST between 1 and 5 x ULN at study start, close observation for DILI 
(as described below) should be considered in subjects with any of the following criteria (all labs 
confirmed by repeat testing):

ALT or AST > 2 x baseline at any time

Total bilirubin > 2 x ULN  

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
ALP > 3 x ULN

INR >1.5 x ULN (except for subjects on anticoagulant therapy)  

Clinical signs or symptoms that are, in the opinion of the investigator, consistent with 
hepatitis (such as right upper quadrant discomfort, fever, nausea, vomiting, jaundice, rash, or 
eosinophilia > 5%).  
Close observation includes:

Repeating liver biochemistries (ALT, AST, ALP, total bilirubin, INR) within 48 hours

Obtaining a more detailed history of symptoms and prior or concurrent disease

Obtaining a history of concomitant drug use (including nonprescription medications and 
herbal and dietary supplement preparations), alcohol use, recreational drug use, and special 
diets

Obtaining a history of exposure to environmental chemical agents

Ruling out other causes of liver disease as needed (obtain viral hepatitis panel, imaging for 
evaluation of biliary tract disease, etc. if required in the opinion of the primary investigator)

Continue to monitor liver biochemistries twice weekly. Frequency can decrease to once a 
week or less if abnormalities stabilize or study drugs have been discontinued and subject is 
asymptomatic
During a period of close observation, study drugs can be continued, if desired, at the discretion 
of the principal investigator. 
However, for all subjects, study drugs should be withheld if any of the following criteria are met:

ALT or AST > 3 x ULN AND either Total bilirubin > 2 x ULN or INR > 1.5 (in subjects not 
on anticoagulation)

ALT or AST > 3 x ULN AND the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)

ALT or AST > 8 x ULN 

ALT or AST > 5 x ULN for more than 2 weeks
AND

No other cause for the combination of laboratory abnormalities is immediately apparent 
(e.g. prolonged INR with warfarin use) important potential causes or contributors to 
abnormal AST/ALT or total bilirubin values include, but are not limited to:
Obstructive gall bladder or bile duct disease

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Viral or alcoholic hepatitis (e.g. hepatitis A/B/C/D/E, Epstein-Barr virus, 
cytomegalovirus, herpes simplex virus, varicella)
Autoimmune hepatitis
Concomitant administration of other hepatotoxins, including excessive doses of 
acetaminophen, drugs that inhibit bilirubin glucuronidation (e.g. indinavir, atazanavir, 
irinotecan), or herbal or dietary supplements
Hypoxic or ischemic hepatopathy or congestive hepatopathy in association with 
significant right-sided heart failure
Wilson disease
Progression of malignancy involving the liver (note that metastatic disease to the liver, by 
itself, should not be used as an explanation for significant AST/ALT elevations)
If study drugs are withheld, they may be reintroduced with approval from the Gilead Medical 
Monitor.
Treatment-emergent toxicities will be noted by the Investigator and brought to the attention of 
the Medical Monitor. Whether or not considered treatment-related, all subjects experiencing AEs 
must be monitored periodically until symptoms subside, any abnormal laboratory values have 
resolved or returned to baseline levels or they are considered irreversible, or until there is a 
satisfactory explanation for the changes observed. Other than in the case of the liver enzymes 
noted above, Grade 3 or 4 clinically significant laboratory AEs should be confirmed by repeat 
testing as soon as practical to do so, and preferably within 3 calendar days of receipt of the 
original test results. 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. Any questions 
regarding toxicity management should be directed to the Medical Monitor.
7.6.
Special Situations Reports
7.6.1.
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 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.

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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).
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.
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
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 DSPH by transmitting electronically and also by sending paper pregnancy 
report form within 24 hours of becoming aware of the pregnancy. 
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3. Furthermore, any SAE occurring as an adverse pregnancy outcome post study must 
be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH using the pregnancy outcome report 
form. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead DSPH. Gilead DSPH contact information is as follows: 
Email: 
 and Fax: 
PPD
PPD

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Pregnancies of female paiiners of male study subjects exposed to Gilead or other study diugs 
must also be repo1ied and relevant infonnation should be submitted to. Gilead DSPH using the 
pregnancy and pregnancy outcome fonns within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been comJ)leted, the outcome should be reJ)orted directly to Gilead DSPH, fax number 
IPIPD 
or email IPD 
Refer to Appendix 3 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements. 
7.6.2.2. 
Repo1iing Other Special Situations 
All special situations repo1is (SSRs) will be recorded in the eCRF database within the timelines 
outlined in the eCRF completion guideline. 
Electronic Special Situations Repo1i ( eSSR) Repo1iing Process 
• 
Site personnel record all SSR data in the eCRF database and from there transmit the SSR 
infonnation to Gilead DSPH within 24 hours of the investigator's knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines. 
• If for any reason it is not possible to record the SSR infonnation electr·onically, i.e., the eCRF 
database is not functioning, record the SSR on the paper serious adverse event repo1iing fonn 
and subinit within 24 hours to: 
Gilead DSPH: Email: IPIPD 
Fax: IPD 
As soon as it is possible to do so, any SSR repo1ied via paper must be tr·anscribed into the eCRF 
Database according to instructions in the eCRF completion guidelines. 
If an SSR has been reported via a paper fo1m because the eCRF database has been locked, no 
fuither action is necessaiy. 
These repo1is must consist of situations that involve study diugs and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concoinitant medications does not need to be repo1ied on 
the special situations repo1i fonn; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be repo1ied on the AE fonn. 
Any inappropriate use of concoinitant medications prohibited by this protocol should not be 
repo1ied as "Inisuse," but may be more appropriately documented as a protocol deviation. 
Refer to Section 7.3 and the eCRF completion guidelines for full instmctions on the mechanism 
of special situations repo1iing. 
All clinical sequelae in relation to these special situation repo1is will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE repo1i fo1m. Details of the symptolilS and 
signs, clinical management, and outcome will be repo1ied, when available. 
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8. 
STATISTICAL CONSIDERATIONS 
Details will be provided in the statistical analysis plan (SAP). 
8.1. 
8.1.1. 
Analysis Objectives and Endpoints 
Analysis Objectives 
The primary objective of this study is as follows: 
• 
To evaluate the safety and tolerability of GS-097 6 in subjects with NASH. 
The explorato1y objectives of this study are as follows: 
8.1.2. 
Primary Endpoint 
The prima1y endpoint is the safety of GS-0976 in subjects with NASH. 
8.1.3. 
Exploratory Efficacy Endpoints 
I 
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8.2.
Analysis Conventions
All individual subject data will be listed as measured.  All statistical summaries and analyses will 
be performed using SAS® software (SAS Institute, Cary, North Carolina, USA).
8.2.1.
Analysis Sets
8.2.1.1.
Efficacy
The primary analysis set for efficacy analysis is defined as the Full Analysis Set (FAS), which 
includes all subjects who were randomized into the study and received at least 1 dose of study 
drugs.
Subjects who receive study drugs other than that to which they were assigned for the entire 
duration of treatment, will be analyzed according to the treatment group they were randomized.
8.2.1.2.
Safety
The primary analysis set for safety analyses is defined as all subjects who received at least 
one dose of study drugs. Subjects who receive study drugs other than that to which they were 
assigned for the entire duration of treatment, will be analyzed according to the study drugs
received.
All data collected during treatment plus 30 days after last dose of study drugs will be included in 
the safety summaries.
CCI

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8.2.1.3. 
Phaimacokinetics 
Final 
Amendment 1 
There are two phaimacokinetic analysis sets: 1) The PK analysis set which includes 
concentration data from the sin le sam les drawn at each visit 
The PK analysis set will include all randomized subjects who took at least one dose of study 
diugs and for whom concentration data of analytes GS-0976 (and its metabolites as applicable) 
are available. The PK analysis set will be used for analyses of population PK. 
8.2.1.4. 
Biomai·kers 
The Biomarker Analysis Set will include data from subjects in the Safety Analysis Set who have 
the necessaiy baseline and on-study measurements to provide interpretable results for the 
specific parameters of interest. 
8.3. 
Data Handling Conventions 
Missing data can have an impact on the inte1p retation of the trial data. In general, values for 
missing data will not be imputed. 
Where appropriate, safety data for subjects that did not complete the study will be included in 
summary statistics. For example, if a subject received study medication, the subject will be 
included in a summaiy of adverse events according to the treatment received; othe1wise, if the 
subject is not dosed then they will be excluded from the summa1y. If safety laborato1y results for 
a subject ai·e missing for any reason at a time point, the subject will be excluded from the 
calculation of summaiy statistics for that time point. If the subject is missing a pre-dose value, 
then the subject will be excluded from the calculation of summaiy statistics for the pre-dose 
value and the change from pre-dose values. 
Values for missing safety laborato1y data will not be imputed; however, a missing baseline result 
will be replaced with a Screening result, if available. If no pre-treatment laborato1y value is 
available, the baseline value will be assumed to be n01mal (ie, no grade [Grade O]) for the 
summary of graded laborato1y abno1malities. 
Values for missing vital signs data will not be imputed; however, a missing baseline result will 
be replaced with a Screening result, if available. 
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8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline measurements will be summarized using standard descriptive 
methods. 
Demographic summaries will include sex, race/ethnicity, and age.
Baseline data will include a summary of body weight, height, body mass index, and 
randomization stratification group (presence or absence of diabetes), and other disease 
characteristic variables.
8.5.
Efficacy Analysis
The biological activity of GS-0976 will be evaluated using radiologic and biochemical endpoints 
and biomarker variables. Because efficacy endpoints will be evaluated for exploratory purpose, 
formal statistical comparisons will not be made for these endpoints. Point estimates and 
ninety-five percent confidence intervals (95% CI) will be provided if applicable.
8.6.
Safety Analysis
All safety data collected on or after the date that GS-0976 was first dispensed up to the date of 
last dose of GS-0976 plus 30 days will be summarized by treatment group. Data for the 
pretreatment and follow-up periods will be included in data listings. 
8.6.1.
Extent of Exposure
Data for a subject’s extent of exposure to GS-0976 will be generated from the study drug 
administration eCRF. Exposure data will be summarized by treatment group. 
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database. Adverse event severity will be graded using the CTCAE 
Version 4.03.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event (TEAE) will be defined as 1 or both of the following:

Any AEs with an onset date on or after the start date of study drugs and no later than 30 days 
after permanent discontinuation of study drug.

Any AEs leading to premature discontinuation of study drugs.
Summaries (number and percentage of subjects) of TEAEs by SOC and PT will be provided. 
Treatment-emergent AEs will also be summarized by relationship to study drug and severity. In 
addition, TEAEs leading to premature discontinuation of study drug and study will be 
summarized and listed.

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All AEs collected during the course of the study will be presented in data listings with a field for 
treatment-emergent event (yes/no). 
8.6.3. 
Laboratory Evaluations 
Selected laborato1y data will be summarized (n, mean, SD, Median, Ql , Q3, minimum, and 
maximum) by treatment group and study visit along with the coITesponding change from 
baseline values. 
Graded laborato1y abnonnalities will be defined using the grading scheme in the CTCAE 
Version 4.03 (refer to Appendix 4). Grading oflaborato1y abnonnalities for analysis purposes 
will be perfonned by the central laborato1y. 
fucidence of treatment-emergent laborato1y abnonnalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline up to and including the date of last dose 
of study diu gs plus 30 days will be summarized by treatment group. If baseline data are missing, 
then any graded abnonnality (ie, at least a Grade 1) will be considered treatment emergent. 
8.6.4. 
Other Safety Evaluations 
The number and percentage of subjects developing antibodies to GS-0976 will be summarized 
by treatment aim. Summary statistics for the 12-lead ECGs perfo1med at Baseline and Week 12 
will be generated. 
8.7. 
Pharmacokinetic Analysis 
Plasma concentrations and phan nacokinetic paraineters (eg, AUCtau, Cmax and Ctau) will be listed 
and summai·ized as appropriate for GS-0976 (and its metabolites as applicable) using descriptive 
statistics. 
Details of the analysis plan will be provided in the phaim acokinetic repo1i ing and analysis plan. 
8.8. 
Biomarker Analysis 
Descriptive statistics of biomarker expression and change from baseline will be provided at each 
sainpling time by treatment. Point estimates and 95% confidence intervals may be calculated. 
8.9. 
Sample Size 
Due to the explorato1y nature of this study, no fo1m al power calculations were used to dete1mine 
sainple size. The number of subjects was chosen based on clinical experience with other similar 
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proof of concept studies. However, assuming that 4% of subjects in the placebo arm (N=25) and 
32% in the GS-0976 20 mg arm (N=50) have a ≥ 30% reduction in MRI-PDFF at Week 12, this 
sample size will provide 80% power to detect the difference based on a two-sided Fisher’s exact 
test at a significance level of 0.05.
8.10.
Data Monitoring Committee
An independent, external data monitoring committee (DMC) that consists of two hepatologists 
and a PhD statistician will review the progress of the study and perform reviews of safety data. 
The DMC will convene once 20 subjects have been randomized and will meet every 3 to 
4 months thereafter to monitor the study for safety events. The DMC will meet on an ad hoc 
basis if there are at least 3 similar Grade ≥ 3 serious, treatment related Common Terminology 
Criteria for Adverse Events (CTCAE) observed in the trial. In the event of two similar Grade 
4-CTCAE treatment related events or one Grade 5-CTCAE treatment related event, the DMC 
will review the data and advise the sponsor regarding stopping or continuing the trial. The DMC 
will 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 DMC may also provide recommendations as needed regarding 
study design.
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.

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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 (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on 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, "Protection of Human Subjects", and 21 CFR, part 56, 
"Institutional Review Boards".
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 
"Financial Disclosure by Clinical Investigators", providing documentation of their financial 
interest or arrangements with Gilead, or proprietary interests in the study drugs 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 (EC) 
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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and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IRB local 
requirements. The consent form will inform subjects about sample retention.
9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form or biological sample submitted to the Sponsor, IRB, 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 randomized in the trial. Subject data will be processed in accordance with all 
applicable regulations. 
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, eCRF, the study drugs, and any other study information, 
remain the sole and exclusive property of Gilead during the conduct of the study and thereafter. 
This information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, IRB
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 randomized

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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 study drugs, including dates of dispensing and 
return;

Record of all AEs and other safety parameters (start and end date, and including causality 
and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, 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 randomized, 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 and the subject has been randomized. Subsequent to data entry, a 
study monitor will perform source data verification within the EDC system. Original entries as 

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well as any changes to data fields will be stored in the audit trail of the system. Prior to database 
lock (or any interim time points as described in the clinical data management plan), the 
investigator will use his/her log in credentials to confirm that the forms have been reviewed, and 
that the entries accurately reflect the information in the source documents. The eCRF 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.
Study Drug Accountability and Return
Gilead recommends that used and unused study drug supplies be returned to the shipping facility 
from which it came for eventual destruction. The study monitor will provide instructions for 
return. If return is not possible, the study monitor will evaluate each study center’s study drug
disposal procedures and provide appropriate instruction for destruction of unused study drug
supplies. If the site has an appropriate standard operating procedure (SOP) for drug destruction
as determined by Gilead QA, the site may destroy used (empty or partially empty) and unused 
study drug supplies in accordance with that site’s approved SOP. A copy of the site’s approved 
SOP will be obtained for central files. 
If study drugs are destroyed on site, the investigator must maintain accurate records for all study 
drugs destroyed. Records must show the identification and quantity of each unit destroyed, the 
method of destruction, and the person who disposed of the study drugs. Upon study completion, 
copies of the study drug accountability records must be filed at the site. Another copy will be 
returned to Gilead.
The study monitor will review study drug supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRB, 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 
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. 
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, eg, attendance at Investigator's Meetings. If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.
9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Monitoring and Oversight of Biomarker Specimens
Biomarker research specimens will be tracked in a manner consistent with Good Clinical 
Practice by a quality-controlled, auditable, and appropriately validated laboratory information 
management system, to ensure compliance with data confidentiality as well as adherence to 
authorized use of specimens as specified in this protocol and in the Informed Consent Form.  

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9.3.4.
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.
9.3.5.
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 ECs. 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
Afzali A, Berry K, Ioannou GN. Excellent posttransplant survival for patients with nonalcoholic 
steatohepatitis in the United States. Liver Transpl 2012;18 (1):29-37.
Bannas P, Kramer H, Hernando D, Agni R, Cunningham AM, Mandal R, et al. Quantitative 
magnetic resonance imaging of hepatic steatosis: Validation in ex vivo human 
livers. Hepatology 2015;62 (5):1444-55.
Bianchi A, Evans JL, Iverson AJ, Nordlund AC, Watts TD, Witters LA. Identification of an 
isozymic form of acetyl-CoA carboxylase. J Biol Chem 1990;265 (3):1502-9.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41.
Dietrich P, Hellerbrand C. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome. 
Best practice & research 2014;28 (4):637-53.
Dowman JK, Tomlinson JW, Newsome PN. Pathogenesis of non-alcoholic fatty liver disease. 
QJM 2010;103 (2):71-83.
Ekstedt M, Hagstrom H, Nasr P, Fredrikson M, Stal P, Kechagias S, et al. Fibrosis stage is the 
strongest predictor for disease-specific mortality in NAFLD after up to 33 years 
of follow-up. Hepatology 2015;61 (5):1547-54.
Faramawi MF, Wildman RP, Gustat J, Rice J, Abdul Kareem MY. The association of the 
metabolic syndrome with QTc interval in NHANES III. Eur J Epidemiol 2008;23 
(7):459-65.
Harriman G, Greenwood J, Bhat S, Huang X, Wang R, Paul D, et al. Acetyl-CoA carboxylase 
inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and 
modulates dyslipidemia in rats. Proc Natl Acad Sci U S A 2016;113 (13):E1796-
805.
Harwood HJ, Jr. Treating the metabolic syndrome: acetyl-CoA carboxylase inhibition. Expert 
opinion on therapeutic targets 2005;9 (2):267-81.
Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial 
fibrillation: the Framingham study. N Engl J Med 1982;306 (17):1018-22.
Kim KH. Regulation of mammalian acetyl-coenzyme A carboxylase. Annu Rev Nutr 
1997;17:77-99.
Koek GH, Liedorp PR, Bast A. The role of oxidative stress in non-alcoholic steatohepatitis. Clin 
Chim Acta 2011;412 (15-16):1297-305.

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Lambert D, Rouger C, Diebold MD, Ramaholimihaso F, Boulagnon C, Nguyen Y, et al. 
[Gastritis due to Helicobacter pylori, an unusual cause of chronic diarrhoea in 
HIV infected patients] [French]. Medecine et maladies infectieuses 2014;44 
(2014):334-8.
Loomba R, Wolfson T, Ang B, Hooker J, Behling C, Peterson M, et al. Magnetic resonance 
elastography predicts advanced fibrosis in patients with nonalcoholic fatty liver 
disease: a prospective study. Hepatology 2014;60 (6):1920-8.
Neuschwander-Tetri BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic 
steatohepatitis: the central role of nontriglyceride fatty acid metabolites. 
Hepatology 2010;52 (2):774-88.
Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 
2007;11 (1):1-16, vii.
Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, et al. Magnetic 
Resonance Elastography vs Transient Elastography in Detection of Fibrosis and 
Noninvasive Measurement of Steatosis in Patients with Biopsy-proven 
Nonalcoholic Fatty Liver Disease [Accepted Manuscript]. Gastroenterology 2016.
Patel JR, Bettencourt R, Cui JY, Salotti J, Hooker J, Bhatt A, et al. Non-invasive quantitative 
decline in liver fat content on MRI and histologic response in nonalcoholic 
steatohepatitis: A secondary analysis of MOZART trial [Abstract 913]. American 
Assoication for the Study of Liver Diseases (AASLD); 2015 13-17 November; 
San Francisco, CA. pp. 659A-60A.
Ratziu V, Massard J, Charlotte F, Messous D, Imbert-Bismut F, Bonyhay L, et al. Diagnostic 
value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver 
fibrosis in patients with non-alcoholic fatty liver disease. BMC gastroenterology 
2006;6:6.
Sumida Y, Niki E, Naito Y, Yoshikawa T. Involvement of free radicals and oxidative stress in 
NAFLD/NASH. Free radical research 2013;47 (11):869-80.
Tong L, Harwood HJ, Jr. Acetyl-coenzyme A carboxylases: versatile targets for drug discovery. 
J Cell Biochem 2006;99 (6).
Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history 
of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. 
Aliment Pharmacol Ther 2011;34 (3):274-85.
Voulgari C, Tentolouris N, Papadogiannis D, Moyssakis I, Perrea D, Kyriaki D, et al. Increased 
left ventricular arrhythmogenicity in metabolic syndrome and relationship with 
myocardial performance, risk factors for atherosclerosis, and low-grade 
inflammation. Metabolism: clinical and experimental 2010;59 (2):159-65.

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Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with 
analysis of risk factors. Hepatology 1990;12 (5):1106-10.
Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, et al. Prevalence of 
nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely 
middle-aged population utilizing ultrasound and liver biopsy: a prospective study. 
Gastroenterology 2011;140 (1):124-31.
Wong RJ, Cheung R, Ahmed A. Nonalcoholic steatohepatitis is the most rapidly growing 
indication for liver transplantation in patients with hepatocellular carcinoma in the 
U.S. Hepatology 2014;59 (6):2188-95.
Yeh MM, Brunt EM. Pathological features of fatty liver disease. Gastroenterology 2014;147 
(4):754-64.

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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table for GS-US-426-3989
Appendix 3.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, 
Tolerability, and Efficacy of GS-0976 in Subjects with Nonalcoholic Steatohepatitis 
GS-US-426-3989, Amendment 1, 15 December 2016 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
PPD 
PPD 
Date 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator N axne (Printed) 
Signature 
Date 
Site Number 
CONFIDEN'ITAL 
Page 78 
15 December 2016 

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Appendix 2.
Study Procedures Table for GS-US-426-3989
Assessments
Screeninga
Baseline / 
Day 1
On-treatment Visits
Follow Up 
Visitb
(± 5 Days)
Week 1
± 3 days
Week 4
± 3 days
Week 8
± 3 days
Week 12/ETb
± 7 days
Clinical Assessments
Written Informed Consentc
X
Determine Eligibility 
X
X
Medical History
X
Historical Liver Biopsy (If 
Available)
X
Physical Examination
X
Xd
Xd
Xd
Xd
Xd
Xd
Vital Signse including Weight
X
X
X
X
X
X
X
Height
X
Waist Circumference 
X
X
12- lead ECG
X
X
X
Ultrasoundf
X
MRE, MRI-PDFF
X
X
FibroScan®g
X
X
SF-36, WPAI, and CLDQ
Questionnairesh
X
X
Adverse Events
X
X
X
X
X
X
X
Concomitant Medications
X
X
X
X
X
X
X
Dispense Study Drugs
X
X
X
Review of Study Drug Dosing 
Compliance (Pill Count)
X
X
X
X
Laboratory Assessments
Subject Fastingi
X
X
X
X
X
X
X

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Assessments
Screeninga
Baseline / 
Day 1
On-treatment Visits
Follow Up 
Visitb
(± 5 Days)
Week 1
± 3 days
Week 4
± 3 days
Week 8
± 3 days
Week 12/ETb
± 7 days
Chemistry, Hematology, 
Coagulation Panel
X
X
X
X
X
X
X
Lipid Profile
X
X
X
X
X
X
Pregnancy Testj
X
X
X
X
X
X
Serum FSHk
X
Single PK Sampling
X
X
X
X
Hemoglobin A1c
X
X
X
Blood and Urine Collection 
(Biomarker)
X
X
X
X
Stool Collection (Biomarker)
X
X
Urine Drug Screeningl
X
HIV-1, HBV & HCVm Serology
X
Genomic Samplen
X
a.
Screening assessments to be completed within 6 weeks prior to Day 1.  The Screening period also may be extended longer under special circumstances with the explicit 
approval of the Gilead Medical Monitor.
b.
Subjects discontinuing treatment at any time for any reason (Early Termination – ET) should complete the procedures listed for the Week 12/ET visit AND the Follow-Up 
visit.
c.
Obtain written informed consent before initiation of any screening procedure.
d.
Symptom-driven physical examination
e.
Vital signs include blood pressure, heart rate, respiration rate, and body temperature.
f.
Ultrasound may be performed if necessary to confirm NAFLD.
g.
Perform FibroScan® if available.
h.
It is recommended that QoL questionnaires be completed prior to any study procedures being performed and prior to the subject seeing a health care provider. Refer to the 
Study Reference Binder for guidance on QoL questionnaire administration for subjects with QoL questionnaires available at Baseline/Day 1.
i.
Subjects must be in a fasted state at least 8 hours prior to blood collection.
j.
Females of childbearing potential only (See Appendix 3). Serum pregnancy test at Screening and urine pregnancy test at all other visits, except Week 1.
k.
l.
Drug screen for amphetamines, cocaine, and opiates (i.e., heroin, morphine).
m.
HCV Ab positive, reflex to HCV RNA. 
n.
CCI
CCI
CCI

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Appendix 3.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a. Definitions of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (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.
b. Definitions 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 medical documentation.
2) Contraceptive Requirements for Female Subjects
a. Study Drug Effects on Pregnancy and Hormonal Contraception
The data of GS-0976 on pregnant women is not available now.  Relevant non-clinical 
reproductive toxicity studies for human pregnancy have not been conducted yet. There are 
insufficient data to exclude the possibility of a clinically relevant interaction between GS-0976 
and hormonal contraception that results in reduced contraception efficacy. Therefore, 
contraceptive steroids are not recommended as a contraceptive method either solely or as a part 
of a contraceptive regimen. Please refer to the latest version of the investigator’s brochure for 
GS-0976 for additional information.
b. Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. They must not rely on hormone-containing contraceptives as a form of 
birth control during the study.  They must have a negative serum pregnancy test at Screening and 
a negative pregnancy test on the check-in visit prior to enrollment. At minimum, a pregnancy test 
will be performed at the end of relevant system exposure. In the event of a delayed menstrual 
period (over one month between menstruations), a pregnancy test must be performed to rule out 
pregnancy.  This is even true for women of childbearing potential with infrequent or irregular 

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periods. Female subjects must agree to one of the following from Screening until 30 days 
following the last dose of the study drugs.

Complete abstinence from intercourse of reproductive potential.  Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual 
lifestyle. 
Or

Consistent and correct use of 1 of the following methods of birth control listed below. 
Intrauterine device (IUD) with a failure rate of <1% per year
Tubal sterilization
Essure micro-insert system (provided confirmation of success 3 months after procedure)
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)
Female subjects must also refrain from egg donation and in vitro fertilization during treatment 
and until at least 30 days after the last dose of the study drugs.
3) Contraceptive Requirements for Male Subjects
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male subject’s seminal fluid.  Therefore, male subjects with female 
partners of childbearing potential must use condoms during treatment until 90 days after the last 
dose of the study drugs.
Male subjects must refrain from sperm donation from clinic admission, throughout the study 
period, and continuing for at least 90 days following the last dose of study drugs.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicide only, and 
lactational amenorrhea method (LAM). Female condom and male condom should not be used 
together.
5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days (90 days of partner of male subject) of last 
study drug dose. Subjects who become pregnant or who suspect that they are pregnant during the 
study must report the information to the investigator and discontinue study drugs immediately. 
Subjects whose partner has become pregnant or suspects she is pregnant during the study must 
report the information to the investigator. Instructions for reporting pregnancy, partner 
pregnancy, and pregnancy outcome are outlined in Section 7.6.2.

GS-0976
Protocol GS-US-426-3989
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 83
15 December 2016
Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) Version 
4.0 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf