A Phase 2, Open-Label, Multicenter, Multi-cohort Study to Investigate the Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-Infection
Phase: PHASE2
Conditions: Hepatitis C Virus Infection
Sponsor: Gilead Sciences

Study Title: 
Sponsor: 
IND No.: 
EudraCT Number: 
Indication: 
Protocol ID: 
Gilead Sciences Medical 
Monitor: 
Protocol Version/Date: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 2, Open-Label, Multicenter, Multi-coh01i Study to 
Investigate the Safety and Efficacy of Ledipasvir/Sofosbuvir 
Fixed Dose Combination in Adolescents and Children with 
Chronic HCV-Infection 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404, USA 
115268 
2014-003578-17 
Hepatitis C Vims Infection 
GS-US-337-1116 
Name: 
Telephone: 
Mobile: 
Fax: 
E-mail: 
Bittoo Kanwar, MD 
PPD 
rpo 
PD 
t-'U 
Original: 
10 July 2014 
Amendment 1.0: 08 October 2014 
CONFIDENTIALITY STATEMENT 
The inf01mation contained in this document, pruiicularly unpublished data, is the prope1iy or 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 dmg 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 necessa1y to obtain infonned consent from those 
persons to whom the dmg may be administered. 

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc.
Amendment 1.0
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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....................................................................15
1.
INTRODUCTION ..............................................................................................................................................18
1.1.
Background ............................................................................................................................................18
1.2.
Ledipasvir/Sofosbuvir Fixed-Dose Combination...................................................................................19
1.3.
Rationale for the Current Study .............................................................................................................20
1.4.
Rationale for Dose Selection of LDV/SOF FDC ...................................................................................20
1.5.
Overall Risk/Benefit Assessment...........................................................................................................21
2.
OBJECTIVES.....................................................................................................................................................22
3.
STUDY DESIGN................................................................................................................................................23
3.1.
Treatment Plan and Regimen .................................................................................................................23
3.1.1.
PK Lead-in ...........................................................................................................................23
3.1.2.
Treatment Phase ...................................................................................................................23
3.2.
Visit Schedule ........................................................................................................................................25
3.2.1.
PK Lead-in ...........................................................................................................................25
3.2.2.
Treatment Phase ...................................................................................................................26
3.3.
Virologic Response-Based Stopping Criteria.........................................................................................26
3.4.
Treatment Discontinuations Criteria ......................................................................................................26
3.5.
Discontinuations.....................................................................................................................................27
3.6.
Pharmacogenomic Substudy ..................................................................................................................27
3.7.
Long-Term Follow-Up...........................................................................................................................27
3.8.
Breakthrough Futility Assessment .........................................................................................................27
4.
SUBJECT POPULATION..................................................................................................................................28
4.1.
Number of Subjects and Subject Selection ............................................................................................28
4.2.
Inclusion Criteria....................................................................................................................................28
4.3.
Exclusion Criteria...................................................................................................................................29
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................31
5.1.
Randomization and Blinding..................................................................................................................31
5.2.
Ledipasvir/Sofosbuvir Fixed-Dose Combination...................................................................................31
5.2.1.
Description and Handling.....................................................................................................31
5.2.2.
Storage and Handling...........................................................................................................32
5.2.3.
Dosage and Administration of LDV/SOF FDC ...................................................................33
5.3.
Study Drug Compliance.........................................................................................................................34
5.4.
Prior and Concomitant Medications.......................................................................................................34
6.
STUDY PROCEDURES ....................................................................................................................................36
6.1.
Subject Enrollment.................................................................................................................................36
6.2.
Screening Assessments ..........................................................................................................................36
6.2.1.
Screening Visit (Day –28 to Day 0) .....................................................................................36
6.3.
PK Lead-in: Treatment Assessments .....................................................................................................38
6.3.1.
Day 1 Visit ...........................................................................................................................38
6.3.2.
Day 3 ....................................................................................................................................39

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6.3.3.
Day 10 – Intensive PK..........................................................................................................39
6.4.
Treatment Phase: Treatment Assessments .............................................................................................41
6.4.1.
Day 1 Visit ...........................................................................................................................41
6.4.2.
Weeks 1 and 2 (3 days) .....................................................................................................42
6.4.3.
Weeks 4 and 8 (3 days) .....................................................................................................43
6.4.4.
Week 12 (3 days) ..............................................................................................................44
6.4.5.
Unscheduled Visit/Early Termination Visit .........................................................................44
6.5.
Post-Treatment Assessments..................................................................................................................46
6.5.1.
4-Week Post-Treatment Visit (5 days)..............................................................................46
6.5.2.
12-Week Post-Treatment Visit (5 days)............................................................................46
6.5.3.
24-Week Post-Treatment Visit (5 days)............................................................................47
6.6.
Procedures and Specifications................................................................................................................47
6.6.1.
Clinical Laboratory Analytes ...............................................................................................47
6.6.2.
Medical History....................................................................................................................48
6.6.3.
Complete Physical Examination...........................................................................................48
6.6.4.
Tanner Pubertal Stage Assessment.......................................................................................48
6.6.5.
Height & Weight Measurement............................................................................................49
6.6.6.
Bone Age Assessment..........................................................................................................49
6.6.7.
Swallowability Assessment..................................................................................................49
6.6.8.
Vital Signs............................................................................................................................49
6.6.9.
Estimated Glomerular Filtration Rate (GFR) .......................................................................49
6.6.10.
Viral Sequencing (Archive)..................................................................................................49
6.6.11.
Pregnancy Testing................................................................................................................50
6.6.12.
Quality of Life Survey (PedsQL™).......................................................................................50
7.
TOXICITY MANAGEMENT............................................................................................................................51
7.1.
Subject Stopping Rules for LDV/SOF FDC ..........................................................................................51
8.
ADVERSE EVENTS MANAGEMENT ............................................................................................................52
8.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................52
8.1.1.
Adverse Events.....................................................................................................................52
8.1.2.
Serious Adverse Events........................................................................................................52
8.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................53
8.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................53
8.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................53
8.2.2.
Assessment of Severity ........................................................................................................54
8.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead or CRO .........................................................................................................54
8.4.
Gilead Reporting Requirements.............................................................................................................56
8.5.
Special Situations Reports......................................................................................................................56
8.5.1.
Definitions of Special Situations..........................................................................................56
8.5.2.
Instructions for Reporting Special Situations.......................................................................57
9.
STATISTICAL CONSIDERATIONS................................................................................................................59
9.1.
Analysis Objectives and Endpoints........................................................................................................59
9.1.1.
Analysis Objectives..............................................................................................................59
9.1.2.
Primary Endpoints................................................................................................................60
9.1.3.
Secondary Endpoints............................................................................................................60
9.2.
Analysis Conventions.............................................................................................................................60
9.2.1.
Analysis Sets ........................................................................................................................60
9.2.2.
Data Handling Conventions .................................................................................................61
9.2.3.
Interim Analysis ...................................................................................................................62
9.3.
Demographic Data and Baseline Characteristics ...................................................................................62

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9.4.
Pharmacokinetic Analysis......................................................................................................................62
9.5.
Safety Analysis.......................................................................................................................................64
9.5.1.
Extent of Exposure...............................................................................................................64
9.5.2.
Adverse Events.....................................................................................................................64
9.5.3.
Laboratory Evaluations ........................................................................................................65
9.5.4.
Other Safety Evaluations......................................................................................................65
9.6.
Efficacy Analysis ...................................................................................................................................66
9.6.1.
Primary Efficacy Analysis....................................................................................................66
9.6.2.
Secondary Efficacy Analysis................................................................................................66
9.6.3.
Subgroup Analysis ...............................................................................................................66
9.7.
Quality of Life Analysis.........................................................................................................................67
9.8.
Data Monitoring Committee ..................................................................................................................67
9.9.
Sample Size............................................................................................................................................67
10.
RESPONSIBILITIES..........................................................................................................................................68
10.1.
Investigator Responsibilities ..................................................................................................................68
10.1.1.
Good Clinical Practice..........................................................................................................68
10.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Approval...............................................................................................................................68
10.1.3.
Informed Consent/Assent.....................................................................................................69
10.1.4.
Confidentiality......................................................................................................................69
10.1.5.
Study Files and Retention of Records ..................................................................................69
10.1.6.
Case Report Forms...............................................................................................................70
10.1.7.
Drug Accountability.............................................................................................................71
10.1.8.
Inspections............................................................................................................................71
10.1.9.
Protocol Compliance............................................................................................................71
10.2.
Sponsor Responsibilities ........................................................................................................................71
10.2.1.
Protocol Modifications.........................................................................................................71
10.2.2.
Study Report and Publications .............................................................................................72
10.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................72
10.3.1.
Access to Information for Monitoring..................................................................................72
10.3.2.
Access to Information for Auditing or Inspections ..............................................................72
10.3.3.
Study Discontinuation..........................................................................................................73
11.
REFERENCES ...................................................................................................................................................74
12.
APPENDICES ....................................................................................................................................................75
Appendix 1.
Investigator Signature Page....................................................................................................76
Appendix 2.
Study Procedures Table..........................................................................................................77
Appendix 3.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............83
Appendix 4.
Tanner Stages .......................................................................................................................107
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................108

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LIST OF IN-TEXT TABLES
Table 5-1.
Disallowed and Concomitant Medications to be Used with Caution .....................................35
Table 9-1.
SOF, GS-331007, and LDV PK Parameters after Once-Daily Administration of 
SOF/LDV in HCV-Infected Adults Subjects (Population PK Analysis from Phase 2 
and 3 Studies) .........................................................................................................................64
LIST OF IN-TEXT FIGURES
Figure 3-1.
Study Schema.........................................................................................................................25

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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404, USA
Study Title: 
A Phase 2, Open-Label, Multicenter, Multi-cohort Study to 
Investigate the Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed 
Dose Combination in Adolescents and Children with Chronic 
HCV-Infection
IND Number:
EudraCT Number:
115268
2014-003578-17
Study Centers:
Approximately 30 sites in the United States, Europe, Australia, and 
New Zealand
Number of Subjects:
Approximately 200 subjects
Target Population:
Adolescents and children (aged 3 to < 18) chronic hepatitis C virus 
(HCV) infection
Treatment Duration:
PK Lead-in – 10 days
Treatment Phase – 12 weeks
Objectives:
The primary objective of the PK Lead-in Phase of this study is:

To evaluate the steady state pharmacokinetics (PK) and confirm 
the dose of LDV/SOF FDC in chronic HCV-infected pediatric 
subjects
The secondary objective of the PK Lead-in Phase of this study is:

To evaluate the safety, tolerability, and antiviral activity of 
10 days of dosing of LDV/SOF FDC in chronic HCV infected 
pediatric subjects
The primary objective of the Treatment Phase of this study is:

To evaluate the safety and tolerability of LDV/SOF FDC for 
12 weeks in chronic HCV-infected pediatric subjects. 

LDVISOFFDC 
Protocol GS-US-337-1116 
Gilead Sciences, Inc. 
Study Design: 
CONFIDENTIAL 
Final 
Amendment 1.0 
The seconda!y objectives of the Treatment Phase ofthis study are: 
• 
To detennine the antiviral efficacy of 12 weeks ofLDV/SOF 
FDC treatment in chronic HCV infected subjects (including the 
impact ofHCV genotype, IL28 genotype, and prior treatment 
experience), as assessed by the prop01i ion of subjects with 
sustained virological response (SVR) 12 weeks after completion 
of treatment (SVR12) 
• 
To determine the antiviral efficacy of 12 weeks ofLDV/SOF 
FDC treatment in chronic HCV-infected subjects, as assessed by 
the prop01iion of subjects with SVR 4 and 24 weeks after 
completion of treatment (SVR4 and SVR24) 
• 
To evaluate the kinetics of circulating HCV RNA during 
treatment and after completion of treatment 
• 
To evaluate the emergence of viral resistance to LDV and SOF 
during treatment and after completion of treatment 
• 
To evaluate the effect of growth and development on pediatric 
subjects during and after treatment 
The explorat01y objective of this study is: 
• 
PD 
Open-label, multi-coh01i, two-part study evaluating the PK, safety, 
and antiviral activity ofLDV/SOF FDC in chronic HCV-infected 
pediatric subjects. 
The study will be divided into 2 parts and will commence with GT -1 
HCV-infected pediatric subjects as follows (subjects with 
GT-2, -4, -5, and -6 will be included once adult data is available, if 
appropriate): 
PK Lead-in Phase: PK Lead-in will evaluate and/or confnm age 
appropriate LDV/SOF FDC doses by analyzing PK, safety, and 
antiviral activity of LDV /SOF FDC through 10 days of dosing for 
each of the three coh01is. Children aged 3 to < 6, children aged 
6 to < 12 years, and adolescents aged 12 to < 18 with years evidence 
of cluonic HCV and HCV RNA ~ 1000 IU/mL at study entiy will be 
evaluated. Subjects must be treatment na'ive to prui icipate in the PK 
Lead-in Phase. 
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Gilead Sciences, Inc.
Amendment 1.0
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Three cohorts of at least 10 subjects each will be sequentially 
enrolled: 

Cohort 1: 12 to < 18 years, old weighing ≥ 45kg

Cohort 2: 6 to < 12 years old 

Cohort 3: 3 to < 6 years old 
The study will start with Cohort 1.  Subjects will receive LDV/SOF 
FDC (90 mg/ 400 mg fixed dose combination tablet or 4 x 22.5 mg/ 
100 mg based on LDV/SOF FDC swallowability assessment) for 
10 days with intensive PK conducted on Day 10.
PK Lead-in subjects in each cohort (Cohorts 1, 2 and 3) will 
immediately enroll in the Treatment Phase as they complete Day 10
of the PK Lead-in Phase. They will continue dosing with LDV/SOF 
FDC with no interruption of study drug administration. Subjects 
rolling over from the PK Lead-in will not be required to perform 
Treatment Phase Screening, Day 1, or Week 1 visits in the Treatment 
Phase.  
Following completion of study treatment in the PK Lead-in of each 
Cohort, intensive PK and safety results of study treatment will be 
reviewed to confirm the appropriateness of the evaluated LDV/SOF 
FDC dose for the Treatment Phase of that Cohort as well as to 
determine the age-appropriate dose to be evaluated in the PK Lead-in 
of the next Cohort.
Treatment Phase: Treatment Phase will be initiated sequentially by 
cohort after confirmation of age-appropriate LDV/SOF FDC dosage 
levels. Subjects who participate in PK Lead-in Phase will 
immediately rollover into Treatment Phase, with no interruption of 
study drug administration, until the appropriateness of the dose is 
confirmed by PK and safety data from the PK Lead-In Phase.  These 
subjects will start at the Week 2 visit of the Treatment Phase. 
Additional subjects will be enrolled in the Treatment Phase of each 
Cohort upon confirmation of the appropriateness of the dose.
Children aged 3 to < 12 years and adolescents aged 12 to < 18 years 
with chronic HCV-infection and a HCV RNA ≥1000 IU/mL at study 
entry (those who were dosed in the PK Lead-in Phase will have met 
these criteria prior to enrollment) will be evaluated. The study will 
commence with GT-1 HCV infected pediatric subjects and will 
subsequently enroll subjects with GT-2, -4, -5, and -6 once adult data 
is available, if appropriate.

LDVISOFFDC 
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Gilead Sciences, Inc. 
Final 
Amendment 1.0 
All subjects emolled in the study will receive the following regimen: 
• 
LDV/SOF FDC for 12 weeks 
The study will emoll both u·eatment-na'ive and u·eahnent experienced 
pediau·ic subjects, with up to 40 subjects allowed to be u·eatment 
experienced. Approximately 200 total subjects, including subjects 
that pmiicipated in the PK Lead-in Phase, will be emolled in 
Treatment Phase as follows: 
• 
Group 1: Approximately 100 adolescent subjects (12 to < 18 yem·s 
of age) 
• 
Group 2: Approximately 100 pediau·ic subjects (3 to < 12 yem·s of 
age) 
The following defmitions will be used for u·eatment experienced 
subjects: 
• 
Interferon intolerant: Subject who discontinued therapy 
(:S 12 weeks total) due to:::: 1 adverse event 
• 
Interferon non-responder: Subject who did not achieve 
undetectable HCV RNA levels while on u·eatment 
• 
Relapse/breakthrough: Subject who achieved undetectable HCV 
RNA dming u·eatment or within 4 weeks of the end of u·eatment 
but did not achieve a sustained virologic response (SVR) 
The study schedule contains the following visits: Screening, Day 1, 
Weeks 1, 2, 4, 8, and 12 dming the u·eatment phase followed by post-
u·eatment visits 4, 12 and 24 weeks after discontinuation of therapy. 
All subjects who do not attain SVR or have viral relapse will be 
encomaged to discuss u·eahnent with standard-of-cm·e (SOC) therapy 
with their healthcm·e provider. 
Substudy and Long-
Pharmacogenomics (PG) Substudy 
Tenn Follow-Up 
PD 
Study: 
CONFIDENTIAL 
Long-Term Follow-up 
Subjects who attain SVR24 or those who do not attain SVR24 and do 
not initiate experimental or approved anti-HCV therapy will be 
followed eve1y 6 months for assessments of growth, quality of life, 
and long-tenn viral suppression (if applicable) in a sepm·ate protocol 
(GS-US-334-1113). This follow-up will continue for 5 yem·s. 
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08 October 2014 

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Diagnosis and Main 
Eligibility Criteria: 
Chronic HCV-infected, treatment-naïve and treatment experienced
(up to 40 subjects), male and female subjects aged 3 to < 18 as 
determined at Day 1. The study will commence with GT-1 
HCV-infected pediatric subjects and will subsequently enroll subjects 
with GT-2, -4, -5 and -6 once adult data is available, if appropriate. 
Inclusion Criteria:

Chronic HCV infection documented by either:
A) a positive anti-HCV antibody test or positive HCV RNA or 
positive HCV genotyping test at least 6 months prior to the 
Day 1 visit, or
B) a liver biopsy performed prior to the Day 1 visit with evidence 
of chronic HCV- infection

HCV RNA ≥ 1000 IU/mL at Screening

For the PK Lead-in Phase:  subjects in Cohort 1 (age 12 to 
< 18 years of age) must weigh ≥ 45 kg

Sexually active subjects must agree to use 2 forms of highly 
effective contraception, as referenced in Appendix 5, for the 
duration of the study and for 30 days (for female subjects) or 
90 days (for male subjects) after the last dose of study medication. 
Females of childbearing potential (as defined in Appendix 5) must 
have a negative pregnancy test at Screening and Day 1.
Exclusion Criteria:

Hematologic or biochemical parameters at screening outside the 
protocol-specified requirements

HIV, acute hepatitis A virus (HAV) or chronic HBV infection

History of or current decompensated liver disease

Hepatocellular carcinoma or other malignancy (with exception of 
certain resolved skin cancers)

Chronic liver disease of a non-HCV etiology 
(eg, hemochromatosis, Wilson’s disease, alpha-1 antitrypsin 
deficiency)

Systemic corticosteroid use for 2 weeks (pulmonary/nasal 
administration is permitted)

Active or recent history (≤ 1 year) of drug or alcohol abuse

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
History or current evidence of any condition, therapy, laboratory 
abnormality or other circumstance that might confound the results 
of the study, or interfere with the subject’s participation for the 
full duration of  the study, such that it is not in the best interest of 
the subject to participate.
See Sections 4.2 and 4.3 of the protocol for full eligibility criteria.
Study Procedures/
Frequency:
PK Lead-in Phase: 
Screening assessments will be completed within 28 days of the Day 1 
visit. 
Screening assessments will include: complete physical examination, 
vital signs (including body height and weight), adverse events (AEs),
concomitant medications, LDV/SOF FDC Swallowability 
Assessment (may be performed at screening up to Day 1), 
hematology, safety laboratory tests, coagulation tests, HCV RNA, 
serum β-human chorionic gonadotropin (hCG - females of 
childbearing potential only), urinalysis, and urine drug screen, IL28B 
genotyping, serology (HIV, HAV, HCV, and HBV), HbA1c, thyroid 
stimulating hormone (TSH), alpha fetoprotein, alpha-1 anti-trypsin.
Study Visits will occur at Screening, Day 1, Day 3, and Day 10.
On-Treatment assessments include physical examination, Tanner 
Pubertal Stage Assessment (Day 1 only), vital signs (including body 
height and weight), bone age assessment (Day 1 only), adverse events 
(AEs), concomitant medications, pregnancy prevention counseling 
(Day 1 only; all subjects ≥ 12 years of age and subjects < 12 years of 
age at the discretion of the Investigator based on subject’s pubertal 
status), quality of life survey (Day 1 only), safety laboratory tests, 
HCV RNA, viral sequencing sampling, and urinalysis.  Coagulation 
testing and urine pregnancy tests (females of child bearing potential 
only) will be performed at Day 1 and Day 10 only. LDV/SOF FDC 
swallowability assessment with placebo will be performed at 
Screening or up to Day 1 to assess a subject’s ability to swallow the 
90 mg/ 400 mg or 22.5 mg/ 100 mg FDC tablet (only subjects 
administered LDV/SOF FDC in tablet form). 
Subjects (at least 10 subjects per cohort) enrolled in the PK Lead-in 
Phase will participate in an intensive PK evaluation on Day 10. 
Following completion of the Day 10 intensive PK visit, subjects will 
then return for scheduled study visits outlined in the Treatment Phase 
and will continue dosing with LDV/SOF FDC with no interruption of 
study drug administration. Subjects will be administered a dosing 
diary with instructions.

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Treatment Phase: 
Screening assessments will be completed within 28 days of the Day 1 
visit. For subjects continuing from PK Lead-in, screening for 
Treatment Phase will not be required.
Screening assessments will include complete physical examination, 
vital signs (including body height and weight), AEs, concomitant 
medications, coagulation, safety laboratory tests, HCV RNA, serum 
β-human chorionic gonadotropin (hCG- females of childbearing 
potential only), urinalysis, urine drug screen, serology (HIV, HAV, 
HCV, HBV), IL28B genotyping, HbA1c, TSH, alpha fetoprotein,
alpha-1 anti-trypsin. LDV/SOF FDC swallowability assessment with 
placebo will be performed at Screening or up to Day 1 to assess a 
subject’s ability to swallow the 90 mg/ 400 mg or 22.5 mg/ 100 mg
FDC tablet (only subjects administered LDV/SOF FDC in tablet 
form).
Study visits will occur at Screening, Day 1, and at the end of 
Weeks 1, 2, 4, 8, and 12. All Treatment Phase subjects will then 
return for follow-up visits at 4, 12 and 24 weeks after discontinuation 
of therapy. 
On-treatment assessments will include physical examination, vital 
signs (including body height and weight), AEs, concomitant 
medications, pregnancy prevention counseling (all subjects ≥12 years 
of age and subjects < 12 years of age at the discretion of the 
Investigator based on subject’s pubertal status), safety laboratory 
tests, coagulation tests, HCV RNA, viral sequencing, urine pregnancy 
tests (females of childbearing potential only), PK samples, and 
urinalysis. Tanner Pubertal Stage assessment will be performed at 
Day 1, end of treatment, post-treatment Week 12, and post-treatment 
Week 24 visits; parental heights will be recorded at Day 1. The Bone 
Age Assessment will be performed at the Day 1 and post-treatment 
Week 24 visits. If available, results from liver biopsies will be 
collected at screening. LDV/SOF FDC swallowability assessment 
will be performed at screening or up to Day 1 to assess a subject’s 
ability to swallow a placebo to match the 90 mg/ 400 mg or 22.5 mg/
100 mg LDV/SOF FDC tablet (only subjects administered LDV/SOF 
FDC in tablet form). For subjects continuing from the PK Lead-in, 
the screening, Day 1, and Week 1 visits of the Treatment Phase will 
not be required. Samples for viral RNA sequencing/phenotyping will 
be collected at Day 1 and every visit thereafter.
Post-treatment assessments will include vital signs (including body 
weight and height), symptom-directed physical examination, AEs 
(only SAEs will be captured at post-treatment Week 12 and 
post-treatment Week 24), concomitant medications (only 

LDVISOFFDC 
Protocol GS-US-337-1116 
Gilead Sciences, Inc. 
Test Product, Dose, 
and Mode of 
Administration: 
Final 
Amendment 1.0 
post-treatment Week 4), safety laborat01y tests, HCV RNA, and urine 
pregnancy tests (only females of childbearing potential at 
post-treatment Week 4 and post-u·eatment Week 12). 
PD 
PKLead-in: 
(Coh01i 1) LDV/SOF FDC is manufactured as a tablet, consisting of 
400 mg SOF and 90 mg LDV, for oral adminisu·ation. LDV/SOF 
FDC tablets will be administered once daily. Subjects unable to 
swallow the LDV/SOF FDC 90 mg/ 400 mg adult tablets (as 
detennined by LDV /SOF FDC Placebo swallowability assessment at 
Screening or at any time during the study) will be re-assigned to 
4 x 22.5 mg/ 100 mg LDV/SOF FDC tablets daily. 
Intensive PK and safety results fi:om the PK Lead-in of each Coh01t 
will be reviewed to confnm the appropriateness of the evaluated 
LDV/SOF FDC dose for the Treatment Phase of that Coh01t as well 
as to dete1mine the age-appropriate dose to be evaluated in the PK 
Lead-in of the next Coh01t. 
Treatment Phase: 
Subjects who prut icipated in PK Lead-in of each Coh01t will continue 
in the Treatment Phase with no intenuption of study dmg 
adminisu·ation until the appropriateness of the dose is confi1med by 
PK and safety data from the PK-Lead-in. Additional subjects will be 
emolled in the Treahnent Phase of each Cohort upon confmnation of 
the appropriateness of the dose. 
Reference Therapy: 
None 
Evaluation Criteria: 
Safety: 
Efficacy: 
PK: 
CONFIDENTIAL 
AEs, laborat01y tests, physical examinations, and vital sign 
measurements will be collected throughout the study. 
Efficacy will be evaluated using scheduled assessments ofHCV RNA 
perf01med using COBAS® AmpliPrep/COBAS® TaqMan® 
HCV Test. 
For subjects in the PK Lead-in, a steady-state PK ofLDV, SOF, and 
its major metabolites (GS-566500 and GS-331007) will be assessed at 
Day 10. For Cohorts 1 and 2, plasma srunples will be collected for PK 
analyses following dosing of study diugs on Day 10 at the following 
time points: 0 (predose), 0.5, 1, 2, 3, 4, 5, 8, and 12 hours postdose 
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(with predose also serving as t= 24). For Cohort 3, plasma samples 
for PK analyses will be collected at the following time points: 
0 (predose), 0.5, 2, 4, 8, and 12 hours postdose (with predose also 
serving as t = 24).
Plasma PK parameters such as Cmax, Tmax, Clast, Tlast, Ctau, AUCtau, and 
t1/2 will be estimated. 
For all subjects in the Treatment Phase, a single PK blood sample will 
be collected at all visits while on treatment. The PK of SOF, 
GS-566500 and GS-331007, and LDV will be assessed.
The effect of age and LDV/SOF FDC dose on PK (SOF, GS-331007,
and LDV) will be explored.
Statistical Methods:
For the PK Lead-in, plasma PK parameters Cmax, Tmax, Clast, Tlast, Ctau, 
AUCtau, and t1/2 will be estimated. The PK parameters will be 
summarized by cohort. The effect of age and LDV/SOF FDC dose on 
PK (SOF, GS-331007, and LDV) will be explored.
For the Treatment Phase, the primary safety endpoint is any AE 
leading to permanent discontinuation of study drug and will be 
summarized by age group, by GT, and by overall. Primary efficacy 
endpoint is SVR12 in all enrolled and treated subjects and will be 
summarized by age group, by GT, by overall, and by age group and 
GT. Point estimate and its 95% confidence interval will be provided. 
Subgroup analysis on SVR12 will be performed by prior treatment 
experience (treatment-naïve vs. treatment experienced) and by GT. 
Other clinically relevant subgroup analyses may be conducted as 
appropriate (i.e., assuming that adequate numbers of patients in these 
subsets are available for analysis). 
All continuous endpoints will be summarized using an 8-number 
summary (n, mean, standard deviation, median, Q1, Q3, minimum, 
and maximum). All categorical endpoints will be summarized by 
number and percentage of subjects who meet the endpoint definition.
Safety endpoints will be analyzed by the number and percent of 
subjects with events or abnormalities for categorical values or 
8-number summary (n, mean, standard deviation, median, Q1, Q3, 
minimum, maximum) for continuous data by age group, by GT, by 
overall, and by age group and GT.
With approximately 100 subjects enrolled into each age group of 
Treatment Phase, a two-sided 95.0% confidence interval of the 
SVR12 rate will extend at most 5.9% in both directions from the 
observed SVR12 rate, assuming the expected SVR12 rate is 90%.
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
AE
adverse event
ALT
alanine aminotransferase (also SGPT)
ANC
absolute neutrophil count
APTT
activated partial thromboplastin time
AST
aspartate aminotransferase  (also SGOT)
AUC
area under the curve
AUCtau
area under the plasma concentration versus time curve over the dosing interval (tau)
BLQ
below the lower limit of quantification
BMI
body mass index
CK
creatine kinase
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
Ctau
observed drug concentration at the end of the dosing interval (tau)
CRF
case report form(s)
CRO
Contract (or clinical) research organization 
DAA
Direct acting antiviral
dL
Deciliter
DNA
deoxyribonucleic acid
DMC
Data Monitoring Committee
DSPH
Drug Safety and Public Health
ECG
Electrocardiogram
eCRF
Electronic case report form(s)
ESA
Erythropoiesis stimulating agent
ESPGHAN
European Society for Paediatric Gastroenterology
EU
European Union
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
Fixed-Dose Combination
FEV1
forced expiratory volume in one second
GCP
Good Clinical Practice (Guidelines)
GCSF
Granulocyte colony stimulating factor
GFR
glomerular filtration rate
GGT
gamma glutamyl transferase
GSI
Gilead Sciences, Inc.
GT
Genotype (viral)
GSI
Gilead Sciences, Inc.
GT
Genotype (viral)
HAV
Hepatitis A Virus

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS (CONTINUED)
Hb
Hemoglobin
HbA1c
Hemoglobin A1c
HBV
Hepatitis B virus
HCV
Hepatitis C virus
HDPE
high-density polyethylene
HIV
Human Immunodeficiency Virus
HLGT
High-Level Group Term
HLT
High-Level Term
ICH
International Conference on Harmonisation
IEC
independent ethics committee
IL28B
IL28B gene
IND
Investigational New Drug (Application)
IRB
institutional review board
IUD
intrauterine device
IWRS
interactive web response system
kg
Kilogram
L
Liter
LDV
Ledipasvir
LLN
lower limit of the normal range
LLOQ
Lower limit of quantification
LLT
Lower-Level Term 
MedDRA
Medical Dictionary for Regulatory Activities
Mg
Milligram
MH
Mantel-Haenszel
mL
Milliliter
Min
Minute
mmHg
millimeters mercury
NS (3/4A/5A/5B)
Non-structural Protein
PBMC
peripheral blood mononuclear cell(s)
PEG
peginterferon alfa-2a
P-gp
P-glycoprotein
PI
Protease inhibitor
PK
Pharmacokinetic
QD
once daily (use only in tables)
RBC
Red blood cell count
RBV
ribavirin
RNA
ribonucleic acid
SADR
Serious adverse drug reaction

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS (CONTINUED)
SAE
serious adverse event
SD
Standard deviation
SOC
Standard-of-Care
SOF
Sofosbuvir
SOP
Standard operating procedure
SUSAR
Suspected Unexpected Serious Adverse Reaction
SVR
Sustained Virologic Response
tmax
The time (observed time point) of Cmax
TSH
Thyroid stimulating hormone
t½
An estimate of the terminal elimination half-life of the drug in serum/plasma/PBMC, 
calculated by dividing the natural log of 2 by the terminal elimination rate constant 
(λz)
ULN
upper limit of the normal range
US
United States
WBC
white blood cell count

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1.
INTRODUCTION
1.1.
Background
Hepatitis C virus (HCV) is responsible for a large proportion of chronic liver disease worldwide 
and accounts for 70% of cases of chronic hepatitis in industrialized countries. The global 
prevalence of chronic hepatitis C is estimated to average 3% {19705}. 
The natural history of chronic HCV-infection in children differs from that in adults since 
HCV-infection in children is relatively benign. Most children chronically infected with HCV are 
asymptomatic or have mild nonspecific symptoms. Clinical symptoms are present in 
approximately 20% of children in the first 4 years of life, with hepatomegaly being the most 
frequent sign (10%). Many, but not all, perinatally infected children will have intermittently or 
persistently abnormal alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 
levels, particularly in the first 2 years of life. In children with vertical HCV-infection who have 
undergone liver biopsy, the histological spectrum is usually mild, although severe liver disease is 
encountered {19801}. Despite the overall more favorable prognosis compared to adults, 
approximately 4% to 6% of children with chronic HCV-infection have evidence of advanced 
fibrosis or cirrhosis and some children eventually require liver transplantation for end-stage liver 
disease as a consequence of HCV-infection {19799}.
The goal of HCV treatment in both pediatric and adult populations is eradication of the virus, 
thereby preventing hepatic inflammation, hepatic fibrosis, cirrhosis, and liver failure resulting in 
either death or need for liver transplantation. This goal, however, is limited by the nature of the 
disease and the fact that not all patients are suitable candidates for currently approved treatments. 
In addition, pediatric treatment is controversial as the current treatment options are limited and 
severe side effects and tolerability can significantly limit or preclude their use. Despite 
well-established guidelines for the treatment of HCV in adults, there is no universal consensus 
on when or if to treat chronic HCV-infection in children. In 2010, the European Society for 
Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) issued guidance for clinical 
trial development for chronic HCV-infection in children {20286}. In the guideline, the 
ESPGHAN suggested that the primary goal of treatment in children is to eradicate the infection 
to prevent late complications. Hence, the goal is not the treatment of an ongoing liver disease, 
but rather the prevention of a future one.
PEG and weight-based RBV are currently considered the SOC for the treatment of 
HCV-infection in children. Current recommendations are that patients with GT-2 or GT-3 be 
treated with PEG+RBV for 24 weeks and those with GT-1 or GT-4 should receive 48 weeks of 
therapy. Successful treatment of GT-1, however, has proved very difficult to achieve in spite of 
additional therapy or increased duration of treatment. A number of pediatric studies have 
reported that despite 48 weeks of treatment, sustained virologic response (SVR24) was observed 
in only 36% to 53% of subjects with GT-1, while response rates were > 80% in subjects with 
GT-2 or GT-3 {20285}.

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Most children treated with PEG+RBV experience at least 1 adverse event due to treatment 
{20285}. Although most of these events are mild to moderate in severity, many of them result in 
dose reductions of 1 or both of the drugs. The most common adverse events have consisted of 
influenza-like illness (91%), headache (62%), and injection site reactions (45%), often leading to 
poor compliance and/or discontinuation from treatment.
Additionally, the concern for growth and development in this age group and the role that both 
PEG and RBV potentially play in reducing growth rates has initiated significant debate among 
pediatric hepatologists as to whether these treatments should even be considered in the pediatric 
population {20282}. Many pediatricians currently advocate delay of treatment past adolescence 
or even into adulthood when options with DAAs are possible {20282}. Unfortunately, in the 25% 
of pediatric patients who do meet the criteria for treatment (elevated transaminases and viral 
loads), the option of PEG+RBV therapy remains inadequate in regard to both efficacy in GT-1 
and safety due to the many risks associated with this treatment.
1.2.
Ledipasvir/Sofosbuvir Fixed-Dose Combination
Ledipasvir/Sofosbuvir fixed-dose combination (LDV/SOF FDC) combines two HCV specific 
direct acting antiviral (DAA) agents into a single tablet for the treatment of chronic 
HCV-infection. SOF is a nucleotide analog that is a potent and selective inhibitor of 
NS5B-directed HCV replication with demonstrated activity against GT 1-6 HCV-infection. 
Ledipasvir (LDV) is a novel HCV NS5A inhibitor that has demonstrated potent anti-HCV 
activity, with the highest activity against GT1 HCV-infection.  
The LDV/SOF phase 3 program consisted of 3 clinical studies: GS-US-337-0102 {28583}, 
GS-US-337-0109 {28585}, and GS-US-337-0108 {28587}. Studies GS-US-337-0102 and 
GS-US-337-0109 evaluated treatment with LDV/SOF FDC RBV for 12 or 24 weeks in 
treatment-naïve and treatment experienced subjects, respectively, infected with GT-1 HCV. Both 
studies enrolled up to 20% of HCV-infected subjects who had documented compensated 
cirrhosis. GS-US-337-0108 evaluated LDV/SOF FDC ± RBV treatment for 8 weeks and 
LDV/SOF FDC treatment for 12 weeks in non-cirrhotic treatment-naïve subjects with GT-1 
HCV-infection. Across these 3 clinical studies, LDV/SOF FDC demonstrated a high degree of 
efficacy (> 93%) for treatment-naïve and treatment experienced subjects with GT-1 
HCV-infection in subjects with and without cirrhosis and achieved their primary efficacy 
endpoints {28583}; {28585}; {28587}. Additionally, treatment with LDV/SOF FDC ± RBV was 
safe and well tolerated in the Phase 3 studies {28583}; {28585}; {28587}.  The inclusion of RBV 
to the treatment regimen was associated with an increase in the total incidence of adverse events 
and in graded laboratory abnormalities of anemia and increased bilirubin. 
Please refer to the Investigator’s Brochure (IB) for additional information on the LDV/SOF FDC 
including:

In Vitro Anti-Hepatitis C Virus Activity

Nonclinical Pharmacokinetics and In Vitro Metabolism

Nonclinical Pharmacology and Toxicology

Clinical Experience

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1.3.
Rationale for the Current Study
This clinical study is designed to evaluate the efficacy and safety of treatment with LDV/SOF 
FDC for adolescents and children with chronic HCV-infection. 
Currently PEG and weight-based RBV are considered the SOC for the treatment of 
HCV-infection in children. Therefore, there is a need for new treatments for HCV in the 
pediatric population that combine potent and sustained efficacy with improved tolerability and 
safety. The primary aim for new treatments of pediatric patients with HCV is to eliminate the 
need to use PEG. In this way, pediatric patients would be able to avoid the necessity of weekly 
injections which can be traumatic and burdensome, and significantly reduce the serious adverse 
events seen with PEG administration. The secondary aim is to eliminate RBV and the adverse 
events seen with its administration. Consequently, LDV/SOF FDC has the potential to be a 
simple and highly effective all-oral treatment regimen for chronic HCV-infection with treatment 
duration of 12 weeks without PEG or RBV for some GTs. 
In vitro viral replicon assay have data demonstrated that LDV has potent, picomolar antiviral 
activity against GT-1a and GT-1b HCV-infection. In the LDV/SOF FDC phase 3 program, 
LDV/SOF FDC without RBV has been shown to have good efficacy and safety in adults infected 
with GT-1 HCV-infection.  In study GS-US-337-0122, a phase 2 open-label study of GT-3 
treatment-naïve adult subjects with and without cirrhosis, LDV/SOF FDC for 12 weeks resulted 
in an SVR12 of 64% whereas LDV/SOF + RBV for 12 weeks resulted in an SVR of 100% 
{29292}.  As a result, the current study which does not include RBV in the treatment regimen 
will initially only enroll pediatric subjects with GT-1 HCV-infection and will not enroll subjects 
with GT-3.
Considering that SOF has pan-genotypic activity and LDV has in vitro, picomolar to nanomolar 
antiviral activity against certain subtypes within GT 4-6 and sub-micromolar antiviral activity 
against certain subtypes within GT-2, studies have been planned and/or initiated with LDV/SOF 
FDC in adult subjects with GT-2, -4, -5, and -6.  If emerging LDV/SOF FDC data in these 
additional GTs support treatment in these genotypes in adults, pediatric subjects with 
GT-2, -4, -5 and -6 will be enrolled in the current study.  Of note, there is an ongoing study 
enrolling GT-2 and -3 pediatric patients, GS-US-334-1112, for treatment with SOF + RBV for 
12 and 24 weeks, respectively.
1.4.
Rationale for Dose Selection of LDV/SOF FDC
Ledipasvir /Sofosbuvir (90 mg/400 mg) fixed-dose combination tablet, administered once daily, 
has demonstrated favorable safety and efficacy profiles in over 1952 HCV-infected subjects 
across different patient populations in phase 2 and 3 clinical trials. These doses are the proposed 
marketed dose of a ledipasvir/sofosbuvir fixed-dose combination tablet for the treatment of 
HCV-infection.
Selection of doses of LDV/SOF FDC for adolescents and younger age groups will target 
systemic exposures similar to those observed in adults at the proposed marketed dose and taking 
into account body weight/body surface area, the potential ontogenic changes in intestinal and 

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hepatically expressed carboxylesterase (CES1) and Cathepsin A (CatA) enzymes, the drug 
transporter p-glycoprotein (Pgp), and the results obtained in older age groups.  Available data 
suggests comparable hepatic expression of CES1 in adolescents and adults with modestly 
decreased expression in children.  However, little is known about the developmental regulation 
of Pgp, CES, and CatA.  As such, the adult clinical doses (90 mg / 400 mg) will be evaluated in 
adolescents (12 to <18 years old).  Safety and PK data in the adolescent group (Cohort 1) in the 
PK Lead-in, in addition to body weight/body surface area will inform dose selection for the
younger age groups.
Age-appropriate formulations of LDV/SOF FDC (a smaller, 22.5 mg / 100 mg strength tablet 
and a non-tablet formulation currently under development) that offer an important option in the 
treatment of HCV-infection in the pediatric population are planned for evaluation in children 
below 12 years of age or children who are unable to swallow the adult dose tablet formulation.
1.5.
Overall Risk/Benefit Assessment
Although the majority of pediatric patients infected with HCV exhibit minimal hepatic sequelae 
despite active viral replication and inflammation, a subset of children and adolescents will 
require treatment. Studies suggest that 3 major categories of disease can occur within 10 years 
after putative HCV exposure: (1) undetectable viremia and normal ALT, (2) persistent yet 
uncomplicated mild liver disease, and (3) progression to end-stage liver disease {20273}. It is the 
last two groups of children in whom therapy may be indicated to prevent end-stage disease, 
either during childhood/adolescence or in early adulthood.
Given that the current SOC for the treatment of children infected with HCV is PEG and RBV 
and these regimens are long in duration, relatively toxic, and not well tolerated, there continues 
to be a need for new treatments for HCV that combine potent and sustained efficacy with 
improved tolerability and safety. 
The combination of LDV plus SOF is anticipated to offer greater antiviral efficacy which could 
result in a shorter treatment duration and/or lead to a regimen without RBV or interferon. These 
in turn could result in reduction in adverse events.  LDV/SOF FDC could also potentially be of 
benefit in patients who have failed prior treatment with SOF+/-RBV+/- PEG.
If high rates of SVR can be obtained with short, well-tolerated regimens, the anticipated 
improvements in safety and tolerability would offer a favorable risk-benefit determination for 
individuals with chronic HCV-infection.

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2. 
OBJECTIVES 
The prima1y objective of the PK Lead-in Phase of this study is: 
Final 
Amendment 1.0 
• 
To evaluate the steady state phrumacokinetics (PK) and confmn the dose ofLDV/SOF FDC 
in chronic HCV-infected pediatric subjects 
The secondruy objective of the PK Lead-in Phase of this study is: 
• 
To evaluate the safety, tolerability, and antiviral activity of 10 days of dosing ofLDV/SOF 
FDC in chronic HCV -infected pediatric subjects 
The primary objective of the Treatment Phase of this study is: 
• 
To evaluate the safety and tolerability ofLDV/SOF FDC for 12 weeks in chronic 
HCV -infected pediatric subjects 
The secondruy objectives of the Treatment Phase of this study ru·e: 
• 
To dete1mine the antiviral efficacy of 12 weeks ofLDV/SOF FDC treatment in chronic 
HCV-infected subjects (including the impact ofHCV genotype, IL28 genotype, and prior 
treatment experience), as assessed by the proportion of subjects with SVR 12 weeks after 
completion of treatment (SVR12) 
• 
To dete1mine the antiviral efficacy of 12 weeks ofLDV/SOF FDC treatment in chronic 
HCV -infected subjects, as assessed by the prop01iion of subjects with SVR 4 and 24 weeks 
after completion of treatment (SVR4 and SVR24) 
• 
To evaluate the kinetics of circulating HCV RNA during treatment and after completion of 
treatment 
• 
To evaluate the emergence of viral resistance to LDV and SOF during treatment and after 
completion of treatment 
• 
To evaluate the effect of growth and development on pediatric subjects during and after 
treatment 
The explorat01y objective of this study is: 
• 
PD 
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3.
STUDY DESIGN
3.1.
Treatment Plan and Regimen
This is an open-label, multi-cohort, two-part study evaluating the PK, safety, and antiviral 
activity of LDV/SOF FDC in chronic HCV-infected pediatric subjects.
3.1.1.
PK Lead-in
The PK Lead-in Phase will evaluate and/or confirm the age appropriate LDV/SOF FDC dose by 
analyzing PK, safety, and antiviral activity of LDV/SOF FDC through 10 days of dosing for each 
cohort. Children aged 3 to < 6 years, children aged 6 to < 12 years, and adolescents aged 12 to 
< 18 years with chronic HCV-infection and a HCV RNA ≥1000 IU/mL at study entry will be 
evaluated. Subjects must be treatment naïve to participate in the PK Lead-in Phase. 
Three cohorts of at least 10 subjects each will be sequentially enrolled: 

Cohort 1:  12 to < 18 years old weighing ≥45kg

Cohort 2:  6 to < 12 years old 

Cohort 3:  3 to < 6 years old 
The study will start with Cohort 1.  Subjects will receive LDV/SOF FDC (90 mg/400 mg adult 
tablet or 4 x 22.5 mg/100 mg tablets if determined necessary based on LDV/SOF FDC
swallowability assessment) for 10 days with intensive PK conducted on Day 10. 
Following completion of study treatment in the PK Lead-in of Cohort 1 and pending PK and 
safety results, the PK Lead-in of Cohort 2 will initiate and receive study treatment (age 
appropriate dose and formulation). Following completion of study treatment in the PK Lead-in of 
Cohort 2 and pending PK and safety results, the PK Lead-in of Cohort 3 will initiate and receive 
study treatment (age-appropriate dose and formulation). 
Subjects enrolled in the PK Lead-in of each cohort (Cohorts 1, 2 and 3) will immediately enroll 
in the Treatment Phase as they complete Day 10 of PK Lead-in.  They will continue dosing with 
LDV/SOF FDC with no interruption of study drug administration.  Subjects rolling over from the 
PK Lead-in Phase will not be required to perform the screening, Day 1, or Week 1 visit of the 
Treatment Phase.
3.1.2.
Treatment Phase
The Treatment Phase will be initiated sequentially by age group as defined in Cohort 1, 2, and 3 
of the PK Lead-in. Subjects who participated in PK Lead-in will immediately rollover into 
Treatment Phase with no interruption of study drug administration until the appropriateness of 
the dose has been confirmed by PK and safety results from the PK Lead-in.  The first visit in the 
Treatment Phase for these subjects will be the Week 2 visit.  Additional subjects will be enrolled 
in the Treatment Phase of each Cohort upon confirmation of the appropriateness of the dose from 
the PK Lead-in.

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Children aged 3 to < 12 years (Group 2) and adolescents aged 12 to < 18 years (Group 1) with 
chronic HCV-infection and a HCV RNA ≥1000 IU/mL at study entry (those who were dosed in 
the PK Lead-in will have met this criteria prior to enrollment) will be evaluated.
Subjects enrolled in the Treatment Phase will receive the regimen of LDV/SOF FDC for 
12 weeks. Subjects with GT 1 will be enrolled first.  If emerging LDV/SOF FDC data in 
GT-2, -4, -5, and -6 support treatment in these GTs in adults, pediatric subjects with GT-2, -4, -5, 
and -6 will be subsequently enrolled.  
The study will enroll both treatment naïve and treatment experienced pediatric subjects with up 
to 40 subjects allowed to be treatment experienced. Approximately 200 total subjects, including 
subjects from the PK Lead-in Phase, will be enrolled in the Treatment Phase as follows:

Group 1: Approximately 100 adolescent subjects (12 to < 18 years of age)

Group 2: Approximately 100 pediatric subjects (3 to < 12 years of age)
The following definitions will be used for treatment experienced subjects:

Interferon intolerant: Subject who discontinued therapy (≤ 12 weeks total) due to ≥1 adverse 
event

Interferon non-responder: Subject who did not achieve undetectable HCV RNA levels while 
on treatment

Relapse/breakthrough: Subject who achieved undetectable HCV RNA during treatment or 
within 4 weeks of the end of treatment but did not achieve a sustained virologic response 
(SVR)
All subjects who do not attain SVR or have viral relapse will be encouraged to discuss treatment 
with SOC therapy with their healthcare provider.

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Figure 3-1.
Study Schema
3.2.
Visit Schedule
3.2.1.
PK Lead-in
Screening assessments will be completed within 28 days of the Day 1 visit. 
Study Visits will occur at Screening, Day 1, Day 3, and Day 10.
Subjects (at least 10 subjects per cohort) enrolled in the PK Lead-in Phase will participate in an 
intensive PK evaluation on Day 10. Subjects will be administered a dosing diary with 
instructions.  
Following completion of the Day 10 intensive PK visit, subjects will then return for scheduled 
study visits outlined in the Treatment Phase and continue dosing with LDV/SOF FDC with no 
interruption of study drug administration.  Subjects rolling over from the PK Lead-in Phase will 
not be required to perform the Treatment Phase screening, Day 1, or Week 1 visits of the 
Treatment Phase.

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3.2.2.
Treatment Phase
Screening assessments will be completed within 28 days of the Day 1 visit. Subjects continuing 
from the PK Lead-in Phase will not be required to complete Screening, Day 1, and Week 1 visits 
of the Treatment Phase.
Study visits for all treatment phase subjects will occur at Screening, Day 1, and the end of weeks 
1, 2, 4, 8, and 12. All subjects will then return for follow-up visits at 4, 12, and 24 weeks after 
discontinuation of therapy.
The total time to complete all study visits is approximately 40 weeks including:

28 day (4 week) screening period

12 week treatment period

24 week post-treatment period
The assessments performed at each visit are described in Section 6.
3.3.
Virologic Response-Based Stopping Criteria
HCV RNA will be unblinded to the Investigator and Sponsor.
The following on-treatment virologic response-based treatment stopping criteria will be utilized:

Confirmed HCV RNA ≥LLOQ after 2 consecutive HCV RNA <LLOQ

Confirmed >1 log10  increase from nadir 

HCV RNA ≥LLOQ through 8 weeks of treatment
Confirmation should be performed as soon as possible but within 2 weeks after determination of 
initial observation.  Subjects that meet the virologic response-based stopping criteria above will 
be notified of their eligibility to participate in the Long-Term Follow-Up Study 
(GS-US-334-1113).
3.4.
Treatment Discontinuations Criteria
The Medical Monitor should be consulted prior to subject discontinuation when medically 
feasible. Study medication must be discontinued in the following instances:

Unacceptable toxicity (as defined in Section 7 of the protocol) or toxicity that, in the 
judgment of the investigator, compromises the ability to continue study-specific procedures 
or is considered to not be in the subject’s best interest.

Pregnancy of female subject or female partner of male subject.

Efficacy failure as defined in Section 3.3.

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• 
Significant protocol violation including non-compliance with study assessments. 
• 
Subject request to discontinue for any reason; it is imp01iant to detennine whether the 
withdrawal of consent is primarily due to an AE, lack of efficacy, or other reason. 
• 
Discontinuation of the study at the request of Gilead, regulat01y agency, or an Institutional 
Review Board (IRB)/Independent Ethics Committee (IEC). 
3.5. 
Discontinuations 
Subjects discontinuing treatment prior to completion of the assigned dosing period should 
complete an Early Tennination visit as described in the Section 6.4.5. 
Subjects who pennanently discontinue the study dmg for any reason including safety and/or 
tolerability concems prior to completion of the assigned dosing period will be followed 
according to the post-u·eatment study assessments described in Section 6.5. 
3.6. 
Pharmacogenomic Substudy 
PD 
3.7. 
Long-Term Follow-Up 
All subjects (those who attain SVR24 or those who do not attain SVR24) who do not initiate 
other experimental or approved anti-HCV therapy will be followed eve1y 6 months for 
assessments of growth, quality of life, and long-te1m viral suppression (if applicable) in a 
separate protocol (GS-US-334-1113). This follow-up study will continue for 5 years. 
3.8. 
Breakthrough Futility Assessment 
A futility assessment will be perf01m ed after the first 10 subjects complete Week 8 on study or 
have viral breakthrough at or prior to Week 8. If3 or more of the first 10 subjects emolled have 
viral breakthrough at or prior to Week 8 or are non-responders (HCV RNA.:::_ LLOQ through 
8 weeks of u·eatment) then fmi her emollment of subjects will be suspended. Virologic 
breakthrough is defined as confnm ed HCV RNA.:::, LLOQ while on u·eatment after two 
consecutive visits with HCV RNA < LLOQ. 
Subjects with known or suspected study dmg non-adherence will not be considered to meet the 
definition of virologic breakthrough, relapse, or non-responder. 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 200 subjects will be enrolled in this study.
In order to manage the total study enrollment, Gilead Sciences, Inc. at its sole discretion, may 
suspend screening and/or discontinue the enrollment at any site at any time (upon written notice 
to the site). Discontinuation of the enrollment phase may result in the immediate ineligibility of 
all subjects screened but not yet enrolled, regardless of the progress or outcome of the screening 
assessments performed.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1. Parent or legal guardian able to provide written informed consent prior to any screening 
evaluations and willing to comply with study requirements.  Subjects will provide assent if 
possible.
2. 3 years to < 18 years of age as determined at Day 1 (consent of parent or legal guardian 
required)
3. PK Lead-in only: subjects in Cohort 1 (age 12 to <18 years of age) must weigh 45 kg
4. PK Lead-in only: all subjects must be treatment naïve: no prior exposure to any IFN, RBV, 
or other approved or experimental HCV-specific DAA agent
5. Treatment experienced subjects:  prior treatment failure to a regimen including interferon 
either with or without RBV that was completed at least 8 weeks prior to Day 1.
i.
Interferon intolerant: Subject who discontinued therapy (≤ 12 weeks total) due to 
≥1 adverse event
ii.
Interferon non-responder: Subject who did not achieve undetectable HCV RNA levels 
while on treatment
iii.
Relapse/breakthrough: Subject who achieved undetectable HCV RNA during treatment 
or within 4 weeks of the end of treatment but did not achieve a sustained virologic 
response (SVR)

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6. Chronic HCV-infection documented by either:
a) a positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test 
at least 6 months prior to the Day 1 visit, or
b) a liver biopsy performed prior to the Day 1 visit with evidence of chronic HCV-infection
7. Infection with HCV as determined at Screening. The study will commence with GT-1 
HCV-infected pediatric subjects and will subsequently enroll subjects with GT-2, -4, -5 
and -6 once adult data is available, if appropriate. 
8. HCV RNA ≥1000 IU/mL at Screening
9. Adequate hematologic function (absolute neutrophil count 1,500/mm3; 
hemoglobin 11 g/dL).
10. Negative serum -HCG pregnancy test (for females of childbearing potential only, as defined 
in Appendix 5)
11. Subject able to provide written assent, if they have the ability to read and write, as 
determined by IRB/IEC/local requirements and Investigator’s discretion
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1. Pregnant or lactating subjects
2. Sexually-active males or females of childbearing potential who are not willing to use an 
effective method of contraception during the study (see Appendix 5 for further details)
3. Infection with GT-3 HCV as determined at Screening.
4. Decompensated liver disease defined as INR 1.2 ULN, platelets 50,000/mm3, serum 
albumin 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g., ascites, 
jaundice, encephalopathy, variceal hemorrhage)
5. Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson’s disease, 
alpha-1 antitrypsin deficiency)
6. -fetoprotein 50 ng/mL
7. Serum creatinine > 1.5 mg/dL
8. Estimated glomerular filtration rate 90 mL/min/1.73m2, as calculated by the Schwartz 
Formula

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9. Evidence of hepatocellular carcinoma (HCC)
10. Co-infection with HIV, acute HAV, or HBV
11. Significant cardiovascular, pulmonary, or neurological disease
12. Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of 
orally administered medications
13. History of solid organ or bone marrow transplantation
14. Chronic daily non-steroidal anti-inflammatory drug therapy
15. Systemic corticosteroid use for 2 weeks (pulmonary/nasal administration is permitted)
16. Investigational agents taken within the past 28 days (except with the expressed approval of 
the Sponsor)
17. Clinically-relevant alcohol or drug abuse within 12 months of screening.  A positive drug 
screen will exclude subjects unless it can be explained by a prescribed medication; the 
diagnosis and prescription must be approved by the investigator
18. Known hypersensitivity to the study drugs, the metabolites, or formulation excipients
19. Any other condition (including alcohol or substance abuse) or prior therapy that, in the 
opinion of the Investigator, would make the subject unsuitable for the study or unable to 
comply with dosing requirements
20. Use of any prohibited concomitant medications as described in Section 5.4 within 28 days of 
the Day 1 visit

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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization and Blinding
Not applicable.
5.2.
Ledipasvir/Sofosbuvir Fixed-Dose Combination
5.2.1.
Description and Handling 
5.2.1.1.
Formulation
LDV/ SOF FDC tablets are orange, diamond-shaped, film-coated tablets containing 90 mg of 
LDV and 400 mg of SOF. The tablets are debossed with “GSI” on one side and “7985” on the 
other side. The LDV/SOF FDC tablets contain the following inactive ingredients: lactose 
monohydrate, copovidone, microcrystalline cellulose, croscarmellose sodium, colloidal silicon 
dioxide, magnesium stearate, polyvinyl alcohol, titanium dioxide, talc, polyethylene glycol, 
FD&C yellow # 6 /sunset yellow FCF aluminium lake.
Placebo to match LDV/SOF FDC 90 mg/ 400 mg tablets for Swallowability Assessment are 
orange, diamond-shaped, film-coated tablets debossed with “GSI” on one side and “7985” on the 
other side. The tablets contain lactose monohydrate, copovidone, microcrystalline cellulose, 
croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, polyvinyl alcohol, 
titanium dioxide, talc, polyethylene glycol, FD&C yellow # 6 /sunset yellow FCF aluminium 
lake.
Age-appropriate formulations of LDV/SOF FDC have been developed for subjects who are 
unable to swallow the LDV/SOF FDC 90 mg/ 400 mg tablets which include a lower dose 
strength tablet (LDV/SOF FDC 22.5 mg/ 100 mg) formulation. LDV/ SOF FDC lower dose 
strength tablets are round, plain-faced, white film-coated tablets containing 22.5 mg of LDV and 
100 mg of SOF. The LDV/SOF FDC lower dose strength tablets contain the following inactive 
ingredients: lactose monohydrate, copovidone, microcrystalline cellulose, croscarmellose 
sodium, colloidal silicon dioxide, magnesium stearate, polyvinyl alcohol, titanium dioxide, talc 
and polyethylene glycol.
Placebos to match LDV/SOF FDC 22.5 mg/ 100 mg tablets for Swallowability Assessment are 
round, plain-faced, white film-coated tablets. The placebo tablets contain the following inactive 
ingredients: lactose monohydrate, copovidone, microcrystalline cellulose, croscarmellose 
sodium, magnesium stearate, polyvinyl alcohol, titanium dioxide, talc and polyethylene glycol.
The non-tablet LDV/SOF FDC formulation will be based on the PK results obtained from 
cohorts 1 and/or 2 of this study. The formulation, composition, acceptability (including 
palatability) will be available and reflected in a protocol amendment which will be submitted for 
approval prior to dosing subjects who are unable to swallow tablets.

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5.2.1.2.
Packaging and Labeling
LDV/ SOF FDC 90 mg/ 400 mg tablets are packaged in white, high density polyethylene 
(HDPE) bottles. Each bottle contains 28 or 30 tablets, a silica gel desiccant, and polyester 
packing material. Each bottle is enclosed with a white, continuous thread, child resistant screw 
cap with an induction-sealed, aluminum faced liner.
Placebo tablets to match LDV/SOF FDC 90 mg/ 400 mg tablets for Swallowability Assessment 
are packaged in white, high density polyethylene (HDPE) bottles. Each bottle contains 30 tablets, 
a silica gel desiccant and polyester packing material. Each bottle is enclosed with a white, 
continuous thread, child resistant screw cap with an induction-sealed, aluminum faced liner.
LDV/SOF FDC 22.5 mg/ 100 mg tablets are packaged in white, high density polyethylene 
(HDPE) bottles. Each bottle contains 30 tablets, a silica gel desiccant, and polyester packing 
material. Each bottle is enclosed with a white, continuous thread, child resistant screw cap with 
an induction-sealed, aluminum faced liner.
Placebo tablets to match LDV/SOF FDC 22.5 mg/ 100 mg tablets for Swallowability Assessment 
are packaged in white, high density polyethylene (HDPE) bottles. Each bottle contains 30 tablets, 
a silica gel desiccant and polyester packing material. Each bottle is enclosed with a white, 
continuous thread, child resistant screw cap with an induction-sealed, aluminum faced liner.
The packaging and labeling of the non-tablet LDV/SOF FDC formulation will be based on the 
chosen formulation. The packaging and labeling will be available and reflected in a protocol 
amendment which will be submitted for approval prior to dosing subjects who are unable to 
swallow tablets.
All LDV/SOF FDC and placebo to match LDV/SOF FDC bottles to be distributed in the US, 
EU, and the rest of the countries shall be labeled to meet all applicable requirements of the 
US Food and Drug Administration (FDA), Annex 13 of Good Manufacturing Practices: 
Manufacture of investigational medicinal products (February 2010), and/or other local 
regulations as applicable.
5.2.2.
Storage and Handling
LDV/ SOF FDC tablets, 90 mg/ 400 mg, should be stored at controlled room temperature until 
required for administration. Controlled room temperature is defined as 25 °C (77 °F); excursions 
are permitted between 15 °C and 30 °C (59 °F to 86 °F).
Placebo to match LDV/ SOF FDC tablets, 90 mg/ 400 mg, for Swallowability Assessment 
should be stored at controlled room temperature until required for administration. Controlled 
room temperature is defined as 25 °C (77 °F); excursions are permitted between 15 °C and 30 °C 
(59 °F to 86 °F).  
LDV/SOF FDC tablets, 22.5 mg/ 100 mg, should be stored at controlled room temperature until 
required for administration. Controlled room temperature is defined as 25 °C (77 °F); excursions 
are permitted between 15 °C and 30 °C (59 °F to 86 °F).

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Placebo to match LDV/ SOF FDC tablets, 22.5 mg/ 100 mg, for Swallowability Assessment 
should be stored at controlled room temperature until required for administration. Controlled 
room temperature is defined as 25 °C (77 °F); excursions are permitted between 15 °C and 30 °C 
(59 °F to 86 °F).
The storage and handling of the non-tablet LDV/SOF FDC formulation will be based on the 
chosen formulation. The storage and handling will be available and reflected in a protocol 
amendment implemented prior to dosing subjects who are unable to swallow tablets.
All drug products should be stored in a securely locked area, accessible only to authorized site 
personnel. To ensure the stability of the Investigational Medicinal Product (IMP) and to ensure 
proper product identification, the drug product should not be stored in a container other than the 
container in which they are supplied. Consideration should be given to handling, preparation, and 
disposal through measures that minimize drug contact with the body. Appropriate precautions 
should be followed to avoid direct eye contact or exposure through inhalation when handling 
LDV/SOF FDC.
Sufficient quantities of LDV/SOF FDC tablets, non-tablet LDV/SOF FDC formulation, and 
placebo tablets will be shipped to the investigator or qualified designee from Gilead Sciences (or 
its designee).
5.2.3.
Dosage and Administration of LDV/SOF FDC
PK Lead-in: (Cohort 1) LDV/SOF FDC 90 mg/ 400 mg tablets will be administered once daily 
with or without food. Subjects determined unable to swallow the placebo to match the 90 mg/ 
400 mg LDV/SOF FDC tablet (by LDV/SOF FDC Placebo Swallowability Assessment at 
Screening up to Day 1) will be re-assigned to 4 x 22.5 mg/ 100 mg tablets daily.  Subjects who 
weigh < 45 kg will be excluded.
Intensive PK and safety results from the PK Lead-in of each Cohort will be reviewed to confirm 
the appropriateness of the evaluated LDV/SOF FDC dose for the Treatment Phase of that Cohort 
as well as to determine the age-appropriate dose to be evaluated in the PK Lead-in of the next 
Cohort.
Treatment Phase: Subjects who participated in the PK Lead-in of each Cohort will continue in 
the Treatment Phase with no interruption of study drug administration until the appropriateness 
of the dose is confirmed by PK and safety data from the PK-Lead-in.  Additional subjects will be 
enrolled in the Treatment Phase of each Cohort upon confirmation of the appropriateness of the 
dose.  
An additional age-appropriate formulation for LDV/SOF FDC Oral Granulates is currently under 
development. The dose for this formulation will be dependent on the PK results obtained from 
Cohorts 1 and/or 2 of this study. The strength, composition, and dosing administration will be 
available and reflected in a protocol amendment which will be submitted for approval prior to 
dosing subjects who are unable to swallow tablets.

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For missed dose(s) of study medication, subjects should be instructed to take the missed dose(s) 
of IMP as soon as possible during the same day.  Subjects should be cautioned never to double 
the next dose with a missed dose of IMP under any circumstances.
5.3.
Study Drug Compliance
Subjects will be instructed to return any unused LDV/SOF FDC in the original container on 
Day 10 (PK Lead-in) and/or at study treatment visits every 4 weeks (Treatment Phase).  
Returned medication will be reconciled by the investigator in order to monitor the subject’s 
compliance with the medication regimen.
5.4.
Prior and Concomitant Medications
Concomitant medications taken within 30 days prior to screening, up to and including 30 days 
after the last dose of study drug, need to be recorded in the source documents and electronic case 
report form(s) (eCRFs).
The following medications are prohibited during the screening period and for a minimum of 
28 days prior to the Day 1 visit through the end of treatment:

Hematologic stimulating agents (e.g., erythropoiesis-stimulating agents (ESAs); granulocyte 
colony stimulating factor (GCSF); thrombopoietin (TPO) mimetics)

Chronic use of systemic immunosuppressants for reasons other than kidney graft 
maintenance including, but not limited to, corticosteroids (prednisone equivalent of 
> 10 mg/day for > 2 weeks), azathioprine, or monoclonal antibodies (e.g., infliximab)

Investigational agents or devices for any indication
Concomitant use of certain medications or herbal/natural supplements (inhibitors or inducers of 
drug transporters ie, P-gp) with study drug(s) may result in PK interactions resulting in increases 
or decreases in exposure of study drug(s). Examples of representative medications which are 
prohibited from 21 days prior to Day 1 through the end of treatment are listed below:

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Table 5-1.
Disallowed and Concomitant Medications to be Used with Caution
Drug Class
Agents Disallowed
Use with Caution
Acid Reducing Agentsa
Proton- Pump Inhibitors, H2-Receptor 
Antagonists, Antacids
Antiarrhythmics b
Quinidine
Anticonvulsantsc
Phenobarbital, Phenytoin, Carbamazepine, 
Oxcarbazepine
Antimycobacterialsc
Rifabutin, Rifapentine, Rifampin
Cardiac Medications b
Digoxin, Valsartan, Olmesartan, 
Telmisartan, Ranolazine, Bosentan
Herbal/Natural 
Supplementsc
St. John’s Wort, Echinaccea, Milk thistle 
(i.e., silymarin), Chinese herb sho-saiko-to 
(or Xiao-Shai-Hu-Tang)
HMG-CoA Reductase 
Inhibitorsd
Rosuvastatin
Atorvastatin, Simvastatin, Pravastatin, 
Pitavastatin, Fluvastatin, Lovastatin
a
It is recommended to separate antacid and LDV/SOF administration by 4 hours. H2-receptor antagonists may be 
administered simultaneously with or staggered from LDV/SOF at a dose that does not exceed doses comparable to 
famotidine 40 mg twice daily.  Proton-pump inhibitor doses comparable to omeprazole 20 mg can be administered 
simultaneously with LDV/SOF or up to 2 hours after taking LDV/SOF. Proton-pump inhibitors should not be taken before 
LDV/SOF. 
b
May result in an increase in the concentration of study drugs and/or concomitant medications. Coadministration of 
LDV/SOF with digoxin may increase the concentration of digoxin. Caution is warranted and therapeutic concentration 
monitoring of digoxin is recommended when coadministered with LDV/SOF. 
c
May result in a decrease in the concentrations of study drugs.
d
Use with study drugs may result in an increase in the concentration of the HMG-CoA Reductase Inhibitors. Monitor for 
signs and symptoms of muscle weakness or myopathy, including rhabdomyolysis.
Medications for disease conditions excluded from the protocol (e.g., active cancer, 
transplantation) are not listed under this Concomitant Medication section and are disallowed in 
the study.

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6.
STUDY PROCEDURES
All subjects will complete screening, on-treatment, and post-treatment assessments. Screening 
assessments will be completed within 28 days of the Day 1 visit. The end of study will occur at 
the 24-week Post-Treatment visit. The schedule of assessments is described below. 
Information on the specific laboratory parameters to be measured and clinical assessments to be 
performed are provided in Section 6.6.
6.1.
Subject Enrollment 
Each candidate’s parent or legal guardian must sign an Informed Consent Form prior to the
conduct of any screening procedures. Each study candidate who has the ability to read and write
must sign an Assent Form, as required by IRB/IEC/local requirements, prior to the conduct of
any study procedures. Screening evaluations will be used to determine the eligibility of each 
candidate for study enrollment. Candidates who fail to meet eligibility criteria by screening 
evaluations may be re-screened once ≥ 30 days after the initial screen if there is a reasonable 
expectation that the candidate will be eligible after repeat screening.
6.2.
Screening Assessments
6.2.1.
Screening Visit (Day –28 to Day 0)
Subjects will complete all screening assessments within 28 days of the Day 1 visit. The screening 
window can be extended to 42 days for subjects requiring additional HCV GT testing or for 
extenuating circumstances.
The following procedures will be performed and documented:

Written informed consent from parent or legal guardian and assent from subject, if applicable 
(see above)

Medical history, including:
— Hepatitis C history
— Hepatitis C treatment history
— Family history, including height and weight of parents
— Liver biopsy results (if available)

Complete physical examination 

Vital signs (temperature, blood pressure, pulse, respiratory rate) and body weight and height

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
Obtain blood samples for tests as listed in Section 6.6.1:
— Hematology
— Chemistry
— Coagulation tests
— HCV RNA
— Determination of HCV viral GT and subtype
— HCV antibody, HIV 1/2 antibody, and HBs antigen, HAV antibody
— HbA1c
— TSH
— IL28B
— Serum -hCG pregnancy test for females of childbearing potential only
— Alpha fetoprotein (AFP)
— Alpha-1 anti-trypsin (ATT)

Obtain urine sample for:
— Urinalysis
— Urine Drug Screen

Review of concomitant medications

Ask subject and/or parent/legal guardian if the subject is able to swallow and tolerate taking 
pills.

Review of all inclusion and exclusion criteria

Perform LDV/SOF FDC swallowability assessment 
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic for the Day 1 visit assessments.

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6.3. 
PK Lead-in: Treatment Assessments 
6.3.1. 
Day 1 Visit 
Final 
Amendment 1.0 
After confnmation of eligibility has been evaluated, the following tests and procedmes must be 
completed prior to emollment and dosing/dispensing on Day 1: 
• 
Perf01m complete physical examination 
• 
Tanner Pubertal Stage Assessment 
• 
Vital signs, including body weight and height measmements 
• 
A single X-ray of the left wrist, hand, and fingers for Bone Age Assessment 
• 
Assessment of AEs and concomitant medications 
• 
Pregnancy prevention counseling including partner pregnancy prevention for male 
pruiicipants (all subj ects ~ 12 yeru·s of age and subjects < 12 yeru·s of age at the discretion of 
the Investigator based on subject's pubertal status) 
• 
Obtain blood samples for: 
-
Hematology 
-
Chemistiy 
-
Coagulation tests 
-
HCVRNA 
-
Viral sequencing (ru·chive) 
_ 
PD 
• 
Obtain mine samples for the following procedmes: 
-
Urinalysis 
-
~ -hCG pregnancy test for females of childberu·ing potential only 
• 
Subject completes quality of life smvey: Subject is to review questionnaire with a 
parent/guardian and write/mru·k answers directly onto the questionnaire. 
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6.3.1.1.
Drug Administration

Dispense study drug as directed by the IWRS

Instruct the subject on the packaging, storage and administration of study drug

Perform LDV/SOF FDC swallowability assessment (for subjects administered LDV/SOF 
FDC in tablet form only if not previously completed at screening).  Observe the subject 
taking the first dose of study drug (with or without food) and record the time of first dose

Subjects will be administered a dosing diary with instructions.
6.3.2.
Day 3
The following procedures/assessments are to be completed on Day 3:

Perform a symptom-directed physical examination as needed

Vital signs, including body weight and height

Assessment of AEs and concomitant medications

Review medication compliance with subject and/or subject’s parent/guardian

Obtain blood samples for:
— Hematology
— Chemistry
— HCV RNA
— Viral sequencing (archive)

Review subject dosing diary
6.3.3.
Day 10 – Intensive PK 
The Day 10 Intensive PK visit should occur on the protocol-specified visit date based on the 
Day 1 visit. For the purposes of scheduling, the Day 10 Intensive PK visit may 
be performed within +3 days of the protocol-specified visit date (subjects will continue daily 
dosing through the Intensive PK Visit).
Subjects should come in a fasted state for the Day 10 Intensive PK visit (i.e., no food or drink 
except water at least 8 hours prior to the Day 10 Intensive PK visit). Subjects and/or 
parents/guardians should be instructed that the Day 10 dose of LDV/SOF FDC must not be taken 
until the evaluations listed below are completed. 

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If the subject has already dosed prior to the Day 10 clinic visit or is not in a fasted state, the 
Day 10 intensive PK assessments must not be completed. The subject and/or parents/guardians 
should be instructed to return in a fasted state within 3 days (Days 11, 12, or 13) for the intensive 
PK visit. 
If dosing non-compliance is identified as per subject dosing diary and pill count on or prior to the 
Day 10 visit, the Day 10 intensive PK assessments must not be completed. The subject and/or 
parents/guardians should be counseled regarding proper dosing and be scheduled to return for the 
Day 10 intensive PK visit no sooner than 3 days following compliant dosing and no later than 
Day 14 (i.e., return on Day 13 or Day 14).  If dosing non-compliance is due to an AE, 
consultation with the Gilead Medical Monitor is required regarding the potential of rescheduling 
the Day 10 intensive PK visit.
In both scenarios described above, the subject and/or parents/guardians should be reminded not 
to take the LDV/SOF FDC prior to arriving at the clinic on the day of the re-scheduled intensive 
PK visit. All Day 10 intensive PK assessments listed below should be completed when the 
subject returns.
The following evaluations are to be completed at the Day 10 Intensive PK visit:

Perform a symptom-directed physical examination 

Vital signs, including body weight and height

Assessment of AEs and concomitant medications

Perform study drug accountability 

Review Subject Dosing Diary

Review medication compliance with subject and/or parent/guardian.

Obtain urine samples for the following procedures:
— Urinalysis
— Urine pregnancy test (females of childbearing potential only). If the urine pregnancy test 
is positive, the Intensive PK sampling will not be completed. The positive result will be 
confirmed with a serum pregnancy test. 

Obtain blood samples for the following laboratory analyses:
— Hematology 
— Chemistry 
— Coagulation tests
— HCV RNA
— Viral sequencing (archive)

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
Perform intensive PK sampling: 
Blood samples will be collected at 0 (predose, ≤30 minutes prior to dosing). After 
collection of the predose sample, subjects will be provided a standardized meal. Within 
5 minutes after consuming the standardized meal, subjects will be dosed with LDV/SOF 
FDC per dosing requirements.
Post-dose blood samples will be collected as follows: 
■
For Cohorts 1 and 2:  0.5, 1, 2, 3, 4, 5, 8, and 12 hours post-dose (with predose also 
serving as t= 24).
■
For Cohort 3 only: 0.5, 2, 4, 8, and 12 hours post-dose (with predose also serving as 
t = 24).
Subjects will be restricted from food intake until after collection of the 4-hour post dose 
blood sample, except for subjects in Cohort 3. Please also refer to the PK manual for 
details about standardized meals and PK sample processing instructions.
After completing the Day 10 intensive PK visit subjects will then continue to the Week 2 visit in 
Treatment Phase (described in Section 6.4.2) with no interruption in dosing.
6.4.
Treatment Phase: Treatment Assessments 
6.4.1.
Day 1 Visit
After confirmation of eligibility has been evaluated, the following tests and procedures must be 
completed prior to enrollment and dosing/dispensing on Day 1:

Perform complete physical examination

Tanner Pubertal Stage Assessment

Vital signs, including body weight and height measurements 

A single X-ray of the left wrist, hand, and fingers for Bone Age Assessment

Review of AEs and concomitant medications

Pregnancy prevention counseling including partner pregnancy prevention for male 
participants (all subjects ≥ 12 years of age and subjects < 12 years of age at the discretion of 
the Investigator based on subject’s pubertal status). 

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• 
Obtain blood samples for: 
-
Hematology 
-
Chemistiy 
-
Coagulation tests 
-
HCV RNA 
-
Viral sequencing (archive) 
_ 
PD 
• 
Obtain urine sample for: 
-
Urinalysis 
-
~ -hCG pregnancy test for females of childbearing potential only 
Final 
Amendment 1.0 
• 
Subject completes quality of life survey: Subject is to review questionnaire with a 
parent/guardian and write/mark answers directly onto the questionnaire 
• 
Perf01m LDV/SOF FDC swallowability assessment (for subjects administered LDV/SOF 
FDC in tablet fonn only if not previously completed at screening) 
6.4.1.1. 
Dmg Adminisu·ation 
• 
Dispense study dmg as directed by the IWRS 
• 
lnstiuct the subject on the packaging, storage, and adminisu·ation of study dmg 
• 
Observe the subject taking the first dose of study dmg (with or without food) and record the 
time of fust dose 
6.4.2. 
Weeks 1 and 2 (± 3 days) 
Subjects who participated in the PK Lead-in will start study visits in the Treatinent Phase at 
Week 2. The following procedures/assessments are to be completed at these visits: 
• 
Vital signs, including body weight and height measurements 
• 
Perf01m symptom-directed physical examination 
• 
Assessment of AEs and concomitant medications 
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
Obtain blood samples for:
— Hematology
— Chemistry
— Coagulation tests
— HCV RNA
— Viral sequencing (archive)
— Single PK 
6.4.3.
Weeks 4 and 8 (3 days)

Vital signs, including body weight and height measurements 

Perform symptom-directed physical examination

Assessment of AEs and concomitant medications

Obtain blood samples for
— Hematology
— Chemistry
— Coagulation tests
— HCV RNA
— Viral sequencing (archive)
— Single PK 

Obtain urine sample for:
— -hCG pregnancy test for females of childbearing potential only

Review medication compliance with subject and/or parent/guardian (subject should return all 
study drugs at these visits)

Dispense study drug as directed by the IWRS

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6.4.4.
Week 12 (3 days)

Perform complete physical examination

Tanner Pubertal Staging Assessment

Vital signs, including body weight and height measurements

Assessment of AEs and concomitant medications

Pregnancy prevention counseling including partner pregnancy prevention for male 
participants (all subjects ≥ 12 years of age and subjects < 12 years of age at the discretion of 
the Investigator based on subject’s pubertal status)

Obtain blood samples for:
— Hematology
— Chemistry
— Coagulation tests
— HCV RNA
— Viral sequencing (archive)
— TSH
— Single PK 

Obtain urine sample for:
— -hCG pregnancy test for females of childbearing potential only

Subject completes quality of life survey: Subject is to review questionnaire with a
parent/guardian and write/mark answers directly onto the questionnaire.

Review medication compliance with subject and/or parent/guardian.

Subjects should return all bottles of study drug at the Week 12 Visit
6.4.5.
Unscheduled Visit/Early Termination Visit
A subject should attend an unscheduled visit if requested by the sponsor or the investigator. The 
assessments are at the investigator’s discretion.
The Sponsor/CRO should be informed when a subject comes off treatment due to an adverse 
event. If a subject discontinues treatment then the assessments outlined below should be 
performed.

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
Perform complete physical examination

Tanner Pubertal Stage Assessment

Vital signs, including body weight and height measurements

Assessment of AEs and concomitant medications

Pregnancy prevention counseling including partner pregnancy prevention for male 
participants (all subjects ≥ 12 years of age and subjects < 12 years of age at the discretion of 
the Investigator based on subject’s pubertal status)

Obtain blood samples for:
— Hematology
— Chemistry
— Coagulation tests
— HCV RNA
— Viral sequencing (archive)
— TSH
— Single PK 

Obtain urine sample for:
— -hCG pregnancy test for females of childbearing potential only

Subject completes quality of life survey: Subject is to review questionnaire with a
parent/guardian and write/mark answers directly onto the questionnaire.

Review medication compliance with subject and/or parent/guardian.

Subjects should return all bottles of study drug at the Early Termination Visit
All subjects should complete Post-Treatment assessments after early termination, as described in 
Section 6.5.
All subjects (those who attain SVR24 or those who do not attain SVR24) who do not initiate 
experimental or approved anti-HCV therapy will be followed every 6 months for assessments of 
growth, quality of life, and long-term viral suppression (if applicable) in a separate protocol 
(GS-US-334-1113). This follow-up will continue for 5 years.

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6.5.
Post-Treatment Assessments
6.5.1.
4-Week Post-Treatment Visit (5 days)

Vital signs, including body weight and height measurements 

Perform symptom-directed physical examination

Assessment of AEs and concomitant medications

Obtain blood samples for: 
— Hematology
— Chemistry
— HCV RNA
— Viral sequencing (archive)

Obtain urine sample for:
— -hCG pregnancy test for females of childbearing potential only

Pregnancy prevention counseling including partner pregnancy prevention for male 
participants (all subjects ≥ 12 years of age and subjects < 12 years of age at the discretion of 
the Investigator based on subject’s pubertal status) 
6.5.2.
12-Week Post-Treatment Visit (5 days)

Vital signs, including body weight and height measurements

Perform symptom-directed physical examination

Assessment of SAEs

Perform Tanner Pubertal Stage assessment

Obtain blood samples for 
— Hematology
— Chemistry
— HCV RNA
— Viral sequencing (archive)

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
Obtain urine sample for:
— -hCG pregnancy test for females of childbearing potential only

Pregnancy prevention counseling including partner pregnancy prevention for male 
participants (all subjects ≥ 12 years of age and subjects < 12 years of age at the discretion of 
the Investigator based on subject’s pubertal status)

Subject completes quality of life survey: Subject is to review questionnaire with a 
parent/guardian and write/mark answers directly onto the questionnaire
6.5.3.
24-Week Post-Treatment Visit (5 days)

Vital signs, including body weight and height measurements 

Perform symptom-directed physical examination

Assessment of SAEs

Tanner Pubertal Stage Assessment

A single X-ray of the left wrist, hand, and fingers for Bone Age Assessment

Obtain blood samples for 
— HCV RNA
— Viral sequencing (archive)

Subject completes quality of life survey: Subject is to review questionnaire with a 
parent/guardian and write/mark answers directly onto the questionnaire.
All subjects (those who attain SVR24 or those who do not attain SVR24) who do not initiate 
other experimental or approved anti-HCV therapy will be followed every 6 months for 
assessments of growth, quality of life, and long-term viral suppression (if applicable) in a 
separate protocol (GS-US-334-1113). This follow-up will continue for 5 years.
6.6.
Procedures and Specifications
6.6.1.
Clinical Laboratory Analytes
Hematology: Hematocrit, Hemoglobin (Hb), Platelet count, Red blood cell count (RBC), White 
blood cell count (WBC) with differential (absolute and percentage) including Lymphocytes, 
Monocytes, Neutrophils, Eosinophils, Basophils, Reticulocyte count and MCV.
Coagulation: INR, Prothrombin time (PT), Activated partial thromboplastin time (APTT) 

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Chemistry Alanine aminotransferase (ALT/SGPT), Aspartate aminotransferase (AST/SGOT), 
Albumin, Alkaline phosphatase, Creatinine, Total Bilirubin (reflex to Direct Bilirubin), Glucose, 
Lipase, Potassium, Sodium, Gamma-glutamyl transferase (GGT), alpha fetoprotein (AFP), 
alpha-1 anti-trypsin, creatine kinase (CK) and amylase.
Urinalysis: Appearance, Blood, Color, Glucose, Leukocyte esterase, pH, Protein, Urobilinogen. 
Reflex to microscopic urinalysis if dipstick result is abnormal.
Virological Tests: Serologies for HCV, HBV and HIV. HCV RNA will be measured using the 
COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 for Use with the High Pure System. 
HCV GT and subtype will be determined using the Siemens VERSANT® HCV Genotype 
INNO-LiPA 2.0 Assay. Gilead reserves the right to use alternate assays for HCV RNA and HCV 
GT should the above assays become unavailable.
IL28B genotype will be determined by polymerase chain reaction (PCR) amplification of the 
SNP, rs12979860, with sequence specific forward and reverse primers and allele specific 
fluorescently labeled TaqMan® MGB probes. Gilead reserves the right to use alternate assays for 
IL28B determination should the above assay become unavailable.
Pregnancy Tests: Serum -hCG, Urine -hCG (if positive, requires immediate confirmation with 
Serum -hCG)
Additional Tests: Urine Drug Screen (for amphetimines, cocaine, methadone, opiates), 
Hemoglobin A1c (HbA1c), TSH (reflex Free T4), Alfa fetoprotein (AFP), Alpha-1 anti-trypsin
(AAT).
6.6.2.
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. Parental heights will be recorded at Day 1.
6.6.3.
Complete Physical Examination
A complete physical examination must include source documentation of general appearance, and 
the following body systems: Head, neck and thyroid; eyes, ears, nose, throat, mouth and tongue; 
chest (excluding breasts); respiratory; cardiovascular; lymph nodes, abdomen; skin, hair, nails; 
musculoskeletal; neurological. 
6.6.4.
Tanner Pubertal Stage Assessment
The Tanner Stage scale is available in Appendix 4.  All subjects will receive a baseline Tanner 
Pubertal Stage Assessment. If the assessment determines that the subject is at a Tanner 5 at 
Day 1, no further Tanner Pubertal Stage Assessments are to be completed. Date of first menses 
will be documented. 

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6.6.5.
Height & Weight Measurement
Height and weight measurement will be collected at each study visit. The difference in body 
weight and height measurements between Day 1 and End of Treatment, post-treatment Week 12, 
and post-treatment Week 24 will be calculated.  
6.6.6.
Bone Age Assessment
A single X-ray of the left wrist, hand, and fingers will be performed at Day 1 Visit and 
post-treatment Week 24.  Local radiologist to determine bone age from x-ray.
6.6.7.
Swallowability Assessment
A LDV/SOF FDC swallowability assessment will be performed at screening up to Day 1.  
Subjects who have indicated that they can take pills will be observed taking a placebo to match 
the 90 mg/ 400 mg LDV/SOF FDC tablet. This will confirm the swallowability of the 90 mg/
400 mg tablet size. If a subject is unable to swallow the 90 mg/ 400 mg LDV/SOF FDC tablet 
size, he/she will repeat the assessment with a placebo for the 22.5 mg/ 100 mg LDV/SOF FDC 
tablet. If unable to swallow the 22.5 mg/ 100 mg LDV/SOF FDC tablet, enrollment of the 
subject will be deferred until the granule formulation is available.
6.6.8.
Vital Signs
Assessment of vital signs will include measurement of resting blood pressure, pulse, respiratory
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 arm supported 
so that the midpoint of the manometer cuff is at heart level;

Use a mercury sphygmomanometer or automatic blood pressure device with an appropriately 
sized cuff with the bladder centered over the brachial artery;

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.
6.6.9.
Estimated Glomerular Filtration Rate (GFR)
Estimated Glomerular Filtration Rate (GFR) using Schwartz Formula (mL/min/1.73m2) = 
k L/Scr [(k is a proportionality constant, for adolescent females ≥12 years old is 0.55; and for 
adolescent males ≥12 years old is 0.70); L is height in centimeters (cm); and Scr is serum 
creatinine (mg/dL)]
6.6.10.
Viral Sequencing (Archive)
Plasma samples will be collected at Day 1 and each subsequent visit for viral sequence analysis. 
Unused samples may be archived.

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6.6.11.
Pregnancy Testing
All females of childbearing potential will have urine pregnancy testing every 4 weeks during the 
dosing period and for a minimum of 30 days following the last dose of LDV/SOF FDC. If 
required by local regulations, additional pregnancy tests beyond 30 days may be added. In the 
event of a positive urine pregnancy result, subjects will be instructed to stop study drugs 
immediately (if applicable) and return to the clinic as soon as possible for a serum pregnancy 
test.
6.6.12.
Quality of Life Survey (PedsQL™)
The PedsQL ™ Pediatric Quality of Life Inventory V4.0 Short Form (SF15) will be completed 
in Treatment Phase of the study at Day 1, End of Treatment, Early Termination (if applicable), 
12-Week Post-Treatment, and 24-Week Post-Treatment visits.  
The PedsQL ™  has separate survey instruments administered by age group, including the Teen 
Report (ages 13-18), Child Report (ages 8-12), Young Child Report (ages 5-7), and Toddlers 
(ages 2-4).  Each survey will be administered to the subject for the current age group at the time 
of survey administration.  

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7.
TOXICITY MANAGEMENT
7.1.
Subject Stopping Rules for LDV/SOF FDC
The Gilead Medical Monitor should be consulted prior to dose discontinuation of LDV/SOF 
FDC unless the investigator believes that immediate action is warranted to ensure the continued 
safety of the subject.
Administration of LDV/SOF FDC may be discontinued due to a clinical or laboratory event. 
There is no option for LDV/SOF FDC dose reduction. If LDV/SOF FDC is stopped for toxicity, 
it should not be restarted.
Subjects who meet any of the following laboratory criteria must stop treatment with LDV/SOF 
FDC:

Elevation of ALT and/or AST >5x Day 1 or nadir, confirmed by immediate repeat testing

Abnormal elevation of ALT >3x Day 1 and total bilirubin >2 x ULN, confirmed by 
immediate repeat testing

Confirmed elevation of ALT >15 x ULN, confirmed by immediate repeat testing

Any Grade 3 or greater rash associated with constitutional symptoms

Any Grade 4 event or lab abnormality assessed as related to treatment with LDV/SOF FDC

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8.
ADVERSE EVENTS MANAGEMENT
8.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
8.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship 
with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or 
disease temporally associated with the use of a medicinal product, whether or not considered 
related to the medicinal product. AEs may also include pre- or post- treatment complications that 
occur as a result of protocol-mandated 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 adverse event and must be reported

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen.

Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions).

Overdose without clinical sequelae (see Section 8.5.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history CRF
8.1.2.
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

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
A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is 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.
8.1.3.
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 IMP 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 8.1.1 and 8.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin).
8.2.
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.
8.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to IMP
therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the investigational 
medicinal product. For SAEs, an alternative causality must be provided (e.g., pre-existing 
condition, underlying disease, intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of AE reporting.

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The relationship to study procedures (e.g., invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the AE has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures (eg., venipuncture)
8.2.2.
Assessment of Severity
The severity grading of AEs will be assessed as Grade 1, 2, 3, or 4 using the GSI Grading Scale 
for Severity of Adverse Events and Laboratory Abnormalities (Appendix 3).
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.
8.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead or CRO
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (CRF/eCRF): all SAEs and adverse events related to 
protocol-mandated procedures.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 4 weeks after last administration of study drug must be reported to the CRF/eCRF database 
as instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
period.
Serious Adverse Events
All SAEs, regardless of causal relationship, that occur 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 24-week post treatment follow-up period, must be 
reported to the CRF/eCRF database and Gilead Drug Safety and Public Health (DSPH) as 
instructed. This also includes any SAEs resulting from protocol-mandated procedures performed
after informed consent is signed 
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30 days of the 
last dose of study IMP, regardless of causality, should also be reported. Investigators are not 
obligated to actively seek SAEs after the 24 week post-treatment follow-up period.  However, if 

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the investigator leam s of any SAEs that occur after study prui icipation has concluded and the 
event is deemed relevant to the use of IMP, he/she should promptly document and rep01i the 
event directly to Gilead DSPH. 
• 
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline. 
Electronic Serious Adverse Event (eSAE) Rep01iing 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 electr·onically, ie, the eCRF 
database is not ftmctioning, record the SAE on the paper serious adverse event rep01i ing 
f01m and submit within 24 hours to: 
Gilead Sciences, Dmg 
Fax: 
+ 1 650 522-5477 
Safety and Public 
E-mail: 
Safety _FC@gilead.com 
Health: 
PRA Intemational 
Fax: 
+1 888 772 6919 (N01ih America); 
Phrumacovigilance 
+49 621 8782 181 (Rest of World) 
Representative: 
E-mail: 
CHOSafety@praintl.com 
Gilead Sciences, 
Name: 
Bittoo Kanwar, MD 
Medical Monitor: 
Phone: 
PPD 
Mobile: 
PPD 
Fax: 
PPD 
E-mail: 
t-'t-'U 
I 
• 
As soon as it is possible to do so, any SAE rep01i ed via paper must be tr·anscribed into the 
eCRF Database according to instructions in the eCRF completion guidelines. 
• If an SAE has been rep01ied via a paper fonn because the eCRF database has been locked, no 
ftnther action is necessruy. 
• 
All AEs and SAEs will be recorded in the CRF/eCRF database within the timelines outlined 
in the CRF/eCRF completion guideline. 
• 
For fatal or life-threatening events, copies of hospital case rep01is, autopsy rep01is, 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. 
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
Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s CRF/eCRF and the event description section of the SAE 
report form.
8.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
8.5.
Special Situations Reports
8.5.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, and pregnancy reports regardless of an 
associated AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 

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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.  
8.5.2.
Instructions for Reporting Special Situations
8.5.2.1.
Instructions for Reporting Pregnancies
The investigator should report all pregnancies that are identified after the subject first consents to 
participate in the study (ie, signs the informed consent) and throughout the study, including the 
post-treatment follow-up period, to Gilead DSPH using the pregnancy report form within 
24 hours of becoming aware of the pregnancy.
Refer to Section 8.3 and the CRF/eCRF completion guidelines for full instructions on the 
mechanism of pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 8.1 and 8.3. Furthermore, any SAE occurring as an adverse pregnancy outcome post 
study must be reported directly 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: 
Safety_FC@gilead.com or Fax: +1 (650) 522-5477.
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead DSPH using the 
pregnancy report form and pregnancy outcome report forms within 24 hours. Monitoring of the 
partner pregnancy should continue until the conclusion of the pregnancy. If the end of the 
pregnancy occurs after the study has been completed, the outcome should be reported directly to 
Gilead DSPH, fax number +1 (650) 522-5477 or email Safety_FC@gilead.com. 
Refer to Appendix 5 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.

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8.5.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead DSPH within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 8.3 and the CRF/eCRF completion guidelines for full instructions on the 
mechanism of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management and outcome will be reported, when available.

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Analysis Objectives and Endpoints 
9.1.1. 
Analysis Objectives 
The prima1y objective ofPK Lead-in Phase of this study is: 
Final 
Amendment 1.0 
• 
To evaluate the steady state phrumacokinetics (PK) and confmn the dose ofLDV/SOF FDC 
in chronic HCV-infected pediatric subjects 
The secondruy objective ofPK Lead-in Phase of this study is: 
• 
To evaluate the safety, tolerability, and viral activity of 10 days of dosing ofLDV/SOF FDC 
in chronic HCV-infected pediatric subjects 
The primru·y objective of Treatment Phase of this study is: 
• 
To evaluate the safety and tolerability ofLDV/SOF FDC for 12 weeks in chronic 
HCV -infected pediatric subjects 
The secondruy objectives of Treatment Phase of this study ru·e: 
• 
To dete1mine the antiviral efficacy of 12 weeks ofLDV/SOF FDC treatment in chronic 
HCV-infected subjects, as assessed by the prop01iion of subjects with SVR 12 weeks after 
completion of treatment (SVR12) 
• 
To dete1mine the antiviral efficacy of 12 weeks ofLDV/SOF FDC treatment in chronic 
HCV-infected subjects (including the impact ofHCV genotype, IL28 genotype and prior 
treatment experience), as assessed by the proportion of subjects with SVR 4 and 24 weeks 
after completion of treatment (SVR4 and SVR24) 
• 
To evaluate the kinetics of circulating HCV RNA during treatment and after completion of 
treatment 
• 
To evaluate the emergence of viral resistance to LDV and SOF during treatment and after 
completion of treatment 
• 
To evaluate the effect of growth and development on pediatric subjects during and after 
treatment 
The explorat01y objective ofthis study is: 
• 
PD 
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9.1.2.
Primary Endpoints
For the PK Lead-in Phase, AUCtau of GS-331007 and LDV are considered the primary PK 
parameters for determining the appropriate LDV/SOF FDC dose.
For the Treatment Phase, the primary safety endpoint is any AE leading to permanent 
discontinuation of study drug (s). The primary efficacy endpoint is SVR12.
9.1.3.
Secondary Endpoints
For the PK Lead-in Phase, the secondary PK endpoints will include early viral kinetics and the 
following PK endpoints: AUCtau, Cmax, AUClast, Tmax, Clast, Tlast, Ctau and t1/2 for 
GS-331007, SOF, and LDV as appropriate. AEs leading to permanent discontinuation of study 
drug(s) will be evaluated as a secondary safety endpoint.
For the Treatment Phase, secondary efficacy endpoints include SVR4, SVR24, breakthrough and 
relapse. Additional efficacy evaluations may include HCV RNA change from Day 1; ALT 
normalization; and viral kinetic parameters. Secondary safety endpoints of growth and 
development measurements will be assessed (e.g. height, weight, and Tanner Stage Assessment).
9.2.
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).
9.2.1.
Analysis Sets 
9.2.1.1.
Pharmacokinetics (PK) Analysis Sets
Intensive PK Analysis Set 
The intensive PK analysis set will include all PK Lead-in subjects who received at least one dose 
of study drug and for whom at least one non-missing PK concentration data, during the intensive 
sampling period, reported by PK lab. The PK analysis set will be used for detailed 
pharmacokinetic analysis of LDV, SOF, and metabolites.  
Sparse PK Analysis Set 
The PK analysis set will include all enrolled subjects who received at least one dose of study 
drug and for whom at least one observed concentration data of LDV, SOF, or GS-331007 are 
available. The PK analysis set will be used for analysis of general PK and single sample plasma
concentrations.

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9.2.1.2.
Safety Analysis Set
The primary analysis set for safety analyses will include subjects who were enrolled and have 
received at least one dose of study drug.
Treatment-emergent data will be analyzed and defined as data collected from the first dose of 
study drug through the date of last dose of study drug plus 30 days.
9.2.1.3.
Efficacy Analysis Set
The analysis set for antiviral activity analyses will be the Full Analysis Set (FAS) which includes 
HCV-infected subjects who were enrolled and have received at least one dose of study drug.
9.2.2.
Data Handling Conventions
Natural logarithm transformation for key PK parameters, such as Cmax and AUCtau, will be 
applied for pharmacokinetic analysis.
The PK concentration values below the limit of quantitation (BLQ) will be treated as zero for the 
determination of summary and order statistics. Individual values that are BLQ will be presented 
as “BLQ” in the concentration data listing and will be excluded in any calculation of geometric 
means or ratios. For the presentation of summary and order statistics, if at least 1 subject has a 
concentration value BLQ for the time point, then the minimum value will be displayed as 
“BLQ”. If more than 50% of the subjects have a concentration data value BLQ for the time 
point, then the minimum and median values will be displayed as “BLQ”. If all subjects have 
concentration data values BLQ for the time point, then all order statistics (minimum, first 
quartile [Q1], median, third quartile [Q3], maximum) will be displayed as “BLQ”.
Missing data can have an impact upon the interpretation of the trial data. Other than the 
endpoints discussed below, in general, values for missing data will not be imputed. 
For the analysis of post-baseline categorical efficacy endpoints, if a data point is missing and is 
preceded and followed in time by values that are deem successes, then the missing data point 
will be termed a success; otherwise the data point will be termed a failure.
Any subject with missing data due to premature discontinuation of the study medication will be 
considered a failure at the time points subsequent to the date of discontinuation. If no HCV RNA 
values are obtained after the last dose of study medication, the subject will be considered a 
treatment failure for the SVR endpoints. 
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 summary of adverse 
events according to the treatment received; otherwise, if the subject is not dosed then they 
will be excluded from the summary.

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
If safety laboratory results for a subject are missing for any reason at a time point, the subject 
will be excluded from the calculation of summary statistics for that time point. If the subject 
is missing a pre-dose value, then the subject will be excluded from the calculation of 
summary statistics for the pre-dose value and the change from pre-dose values.
Values for missing safety laboratory data will not be imputed; however, a missing baseline result 
will be replaced with a screening result, if available. If no pre-treatment laboratory value is 
available, the baseline value will be assumed to be normal (i.e., no grade [Grade 0]) for the 
summary of graded laboratory abnormalities.
Values for missing vital signs data will not be imputed; however, a missing baseline result will 
be replaced with a screening result, if available.
HCV RNA values below the LLOQ for the assay will be set to the lower limit minus 1 for 
calculation of summary statistics for the actual HCV RNA values and the change from baseline 
values by study visit. The reported values will be provided in the HCV RNA listing.
For selected analyses of early time point data, HCV RNA data (IU/mL) may be transformed to 
the logarithmic (base 10) scale (log10 IU/mL).
9.2.3.
Interim Analysis
No formal interim analyses are planned for this study.
9.3.
Demographic Data and Baseline Characteristics
Demographic and baseline measurements will be summarized using standard descriptive 
methods by age group and overall for PK Lead-in and Treatment Phase respectively. 
Demographic data will include sex, self-identified race/ethnicity, and age.
Baseline characteristic data will include body weight, height, body mass index, HCV RNA level 
(log10 IU/mL), HCV GT, prior treatment experience, and additional endpoints as necessary.
9.4.
Pharmacokinetic Analysis
PK analysis will be performed for PK Lead-in using the intensive PK analysis set. The 
concentration data of LDV, SOF, and metabolites (GS-566500 and GS-331007) over sampling 
time will be listed and summarized by nominal time and cohort. Pharmacokinetic parameters 
(e.g., AUCtau, AUClast, Cmax, Tmax, Clast, Tlast, Ctau, λz, CL/F, Vz/F and t½) will be listed and 
summarized for LDV, SOF,  and metabolites (as applicable) using descriptive statistics 
(e.g., sample size, arithmetic mean, geometric mean and its 95% confidence interval, coefficient 
of variation %, standard deviation, median, Q1, Q3, minimum, and maximum) by cohort and 
overall. Plasma concentrations over time will be plotted in semilogarithmic and linear formats as 
mean ± standard deviation and median (Q1, Q3).

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To evaluate if the exposures of LDV and GS-331007 achieved in pediatric subjects of this study 
are similar to the exposures observed in adult subjects (Table 9-1). The LDV and GS-331007
exposure data from this study will be compared to the integrated adult data. The primary 
endpoint of this analysis will be evaluated by carrying out an analysis of variance (ANOVA) for 
log-transformed GS-331007 AUCtau and LDV AUCtau. The secondary endpoints of this analysis 
will be the Cmax of LDV and GS-331007 and Ctau of LDV. The 90% confidence intervals will be 
constructed for the ratio of geometric means of each PK parameters. The equivalence boundary 
is set as 50% to 200%.  
Given that dose ranging studies for SOF established that a dose of 200 mg results in suboptimal 
exposure compared to the 400 mg dose, and the lack of clinically significant exposure-safety 
relationships observed across a broad range of GS-331007 exposure, bounds of 50% to 200% for 
GS-331007 AUCtau will allow identification of a clinically relevant difference in exposure in the 
pediatric population.
A phase 2 study evaluating LDV doses of 30 or 90 mg LDV in combination with DAAs 
VDV+TGV+RBV suggested LDV exposure may be suboptimal at the 30 mg dose based on the 
incidence of virologic breakthrough being approximately half in the 90 mg arm; as such the 
90 mg dose was selected for further development.  In the 90 mg LDV arm of this study, the LDV 
AUCtau at the 25 percentile was 3230 hr*ng/mL.  While this value is 62% lower than the mean 
LDV AUCtau (8530 hr*ng/mL) observed in adult HCV-infected subjects in the LDV/SOF FDC 
Phase 2/3 population, it provides ~99.8% of maximal viral load reduction (exposure-response 
model established in the monotherapy proof of concept study).  In the Phase 2/3 population when 
administered the LDV/SOF FDC, there was a lack of clinically significant exposure-efficacy or 
safety relationships observed across the broad range of LDV exposure.  Taken together these 
data support the utility of bounds of 50% to 200% for LDV AUCtau to identify a clinically 
relevant difference in LDV exposure in the pediatric population.      
In all pediatric age groups, the targeted exposures for GS-331007 and LDV are the adult 
equivalent for which safety and efficacy has been established.  In the absence of any pediatric 
PK information (ie., variability and exposure of GS-331007 or LDV is unknown) assuming a 
2-fold higher  variability, or a 30 % difference in GS-331007 or LDV AUCtau in the pediatric 
population compared to adults, the predicted 90% CIs of the geometric mean ratio (GMR) will 
be contained within the bounds of 50% to 200%.
Individual patient management will be performed by maintaining exposures comparable to 
adults.  In the event more than one subject in each cohort exhibits LDV (AUCtau) or GS-331007 
(AUCtau) exposures less than the 2.5th percentile of adult values, a dose assessment may be 
require for the cohort as appropriate.
The effect of age and LDV/SOF FDC dose on PK (LDV, SOF and GS-331007) will be assessed.

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Table 9-1.
SOF, GS-331007, and LDV PK Parameters after Once-Daily 
Administration of SOF/LDV in HCV-Infected Adults Subjects 
(Population PK Analysis from Phase 2 and 3 Studies) 
Mean (%CV) PK Parametera
GS-331007 (N=2113)
LDV (N=2113)
AUCtau (ng•h/mL)
12,500 (29.2)
8530 (60.8)
Cmax (ng/mL)
736 (28.2)
364 (51.4)
Ctau (ng/mL)
N/A
247 (59.2)
a
Pharmacokinetic parameters are presented as mean (%CV) and are shown to 3 significant digits.
9.5.
Safety Analysis
Safety analysis will be performed for PK Lead-in and overall study Treatment Phase
respectively. Safety data will be summarized by age group, by GT, by overall and by age group 
and GT.
Safety will be evaluated by assessment of clinical laboratory tests, physical examinations, vital 
signs measurements, and by the documentation of AEs.
All safety data collected while on or after the first dose of study drug administration up to 
30 days after the last dose of study drug will be summarized by cohort according to the study 
drug received.
Safety endpoints will be analyzed by the number and percent of subjects with events or 
abnormalities for categorical values or 8-number summary (n, mean, standard deviation, median, 
Q1, Q3, minimum, maximum) for continuous data.
9.5.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug 
administration page of the CRF. Exposure data will be summarized.
9.5.2.
Adverse Events
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). System Organ Class (SOC), High-Level Group Term (HLGT), 
High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be attached to 
the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event will be defined as any new or worsening adverse event that begins on or after the 
date of first dose of study drug up to the date of last dose of study drug plus 30 days. 

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Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC 
and preferred term) will be provided by cohort:

All AEs,

All study drug-related AEs,

Combined Grade 2, 3 and 4 AEs,

Combined Grade 3 and 4 AEs,

Combined Grade 2, 3 and 4 study drug-related AEs,

Combined Grade 3 and 4 study drug-related AEs,

All AEs that caused permanent discontinuation from study drug,

All AEs that caused change in dose or temporary interruption of study drug,

All SAEs (including death), and

All study drug-related SAEs
All AEs collected during the course of the study will be presented in data listings.
9.5.3.
Laboratory Evaluations
Selected laboratory data will be summarized using only observed data. Absolute values and 
changes from baseline at all scheduled visits will be summarized. Graded laboratory 
abnormalities will be defined using the grading scheme in Grading of Laboratory Abnormalities 
provided in Appendix 3. Incidence of treatment-emergent laboratory abnormalities, defined as 
values that increase by at least one toxicity grade from baseline at any time post baseline up to 
and including the date of last dose of study drug plus 30 days, will be summarized by age group 
and overall. If baseline data are missing, then any graded abnormality (i.e., at least a Grade 1) 
will be considered treatment emergent.
All laboratory abnormalities will be included in the listings of laboratory data.
9.5.4.
Other Safety Evaluations
9.5.4.1.
Tanner Pubertal Stage Assessment
Tanner Stages (Appendix 4) will be summarized by baseline Tanner Stage using frequency and 
percentage. Age of first menses will be summarized descriptively.

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9.5.4.2. 
Vital Signs (including Body Weight and Height) 
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Vital signs including body weight and height and change from baseline will be summarized at 
each visit by age group, by GT, by overall and by age group and GT. 
9.6. 
Efficacy Analysis 
Efficacy will be evaluated using scheduled assessments of HCV RNA perf01m ed using CO BAS® 
TaqMan® HCV Test, v2.0 for use with the High Pure System. 
Efficacy analysis will be perf01m ed by age group, by GT, by overall, and by age group and GT 
for Treatment Phase. 
All continuous endpoints will be summarized using an 8-number summruy (n, mean, standru·d 
deviation, median, Ql , Q3, minimum, maximum). All categorical endpoints will be summru·ized 
by number and percentage of subjects who meet the endpoint definition. 
9.6.1. 
Primary Efficacy Analysis 
The primary efficacy endpoint is SVR12 (HCV RNA < LLOQ 12 weeks after completion of 
treatment) in the F AS population. Point estimate and its 95% confidence interval will be 
provided. 
9.6.2. 
Secondary Efficacy Analysis 
For the PK Lead-in Phase, senun HCV RNA actual values and change from baseline will be 
summarized at each visit. 
For the Treatment Phase, the proportion of subjects with HCV RNA below LLOQ over time 
(including SVR endpoints SVR4 and SVR24) will be presented in tabulru· and graphical f01m . In 
addition, descriptive summaries and listings will be provided for additional efficacy evaluations 
including senun HCV RNA actual values and change from baseline, prop01iion of subjects with 
virologic failures, and other endpoints of interest including AL T n01m alization. 
PD 
9.6.3. 
Subgroup Analysis 
Subgroup analysis on SVR12 will be perf01m ed by treatment experience (treatment-naive vs. 
treatment experienced), by IL28 genotype, by GT, and by u·eatment experience and GT. Other 
clinically relevant subgroup analyses may be conducted as appropriate (i.e., assuming that 
adequate munbers of subjects in these subsets ru·e available for analysis). 
Details on efficacy analyses will be described in the statistical analysis plan. 
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9.7.
Quality of Life Analysis
The data from PedsQL ™ Pediatric Quality of Life survey will be summarized by visit and age 
group and overall.
9.8.
Data Monitoring Committee
An external multidisciplinary data monitoring committee (DMC) will review the progress of the 
study and perform interim reviews of safety and provide recommendation to Gilead about 
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’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.
9.9.
Sample Size
With approximately 100 subjects enrolled into each age group of Treatment Phase, a two-sided 
95.0% confidence interval of the SVR12 rate will extend at most 5.9% in both directions from 
the observed SVR12 rate, assuming the expected SVR12 rate is 90%.

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10.
RESPONSIBILITIES
10.1.
Investigator Responsibilities
10.1.1.
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. For studies conducted under a United States IND, the investigator 
will ensure that the basic principles of “Good Clinical Practice,” as outlined in 21 CFR 312, 
subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, part 50, 1998, and 21 CFR, 
part 56, 1998, are adhered to.
Since this is a “covered” clinical trial, the investigator will ensure that 21 CFR, Part 54, 1998, is 
adhered to; a “covered” clinical trial is any “study of a drug or device in humans submitted in a 
marketing application or reclassification petition subject to this part that the applicant or FDA 
relies on to establish that the product is effective (including studies that show equivalence to an 
effective product) or that make a significant contribution to the demonstration of safety.” This 
requires that investigators and all subinvestigators must provide documentation of their financial 
interest or arrangements with Gilead Sciences, or proprietary interests in the drug being studied. 
This documentation must be provided before participation of the investigator and any 
subinvestigator. The investigator and subinvestigator agree to notify Gilead Sciences of any 
change to reportable interests during the study and for one year following completion of the 
study. Study completion is defined as the date that the last subject has completed the protocol 
defined activities.
This study is also subject to and will be conducted in accordance with 21 CFR, part 320, 1993, 
“Retention of Bioavailability and Bioequivalence Testing Samples.”
10.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Approval
This protocol 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/assent) will be submitted by the investigator to an IRB (for studies conducted in the 
United States) or IEC (for studies conducted outside of the United States). Approval from the 
IRB or IEC must be obtained before starting the study and should be documented in a letter to 
the investigator specifying the protocol number, protocol version, protocol date, documents 
reviewed, and date on which the committee met and granted the approval.
Any modifications made to the protocol after receipt of IRB or IEC approval must also be 
submitted to the IRB or IEC for approval before implementation.

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10.1.3.
Informed Consent/Assent
The investigator is responsible for obtaining written informed consent from the parent/legal 
guardian of the subject participating in this study after adequate explanation to the parent/legal 
guardian and subject of the aims, methods, objectives, and potential hazards of the study and 
before undertaking any study-related procedures. Written assent should be obtained from the 
subject as required by IRB/IEC/local requirements for this age population.  The investigator must 
utilize an IRB- or IEC-approved consent/assent form for documenting written informed 
consent/assent. Each informed consent/assent will be appropriately signed and dated by the 
subject or the subject’s parent/legally authorized representative and the person obtaining 
consent/assent.
10.1.4.
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, and an 
identification code (i.e., not names) should be recorded on any form or biological sample 
submitted to the Sponsor, IRB or IEC, or laboratory. The investigator must keep a screening log 
showing codes, names, and addresses for all subjects screened and for all subjects enrolled in the 
trial.
The investigator agrees that all information received from Gilead Sciences, including but not 
limited to the Investigator Brochure, this protocol, CRFs, the investigational new drug, and any 
other study information, remain the sole and exclusive property of Gilead Sciences 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 Sciences. 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.
10.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, CRF and query forms, IRB 
or IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data are listed in the Source Data verification Plan, and 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, i.e., history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);

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
Participation in trial (including trial number);

Trial 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 trial medication (preferably drug dispensing 
and return should be documented as well);

Record of all AEs and other safety parameters (start and end date, and preferably including 
causality and intensity);

Concomitant medication (including start and end date, dose if relevant; dose changes should 
be motivated);

Date of trial completion and reason for early discontinuation, if applicable.
All clinical study documents must be retained by the investigator until at least 2 years after the 
last approval of a marketing application in an ICH region (i.e., United States, Europe, or Japan) 
and until there are no pending or contemplated 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 required by applicable regulatory requirements, by local 
regulations, or by an agreement with Gilead Sciences. The investigator must notify 
Gilead Sciences 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 Sciences must be notified in advance.
If the investigator cannot guarantee this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead Sciences 
to store these in sealed containers outside of the site so that they can be returned sealed to the 
investigator in case of a regulatory audit. When source documents are required for the continued 
care of the subject, appropriate copies should be made for storage outside of the site.
Biological samples at the conclusion of this study may be retained in storage by the Sponsor for 
a period up to 15 years for purposes of this study.
10.1.6.
Case Report Forms
For each subject enrolled, a CRF (or eCRF) must be completed and signed by the principal 
investigator or subinvestigator (as appropriate) within a reasonable time period after data 
collection. This also applies to records for those subjects who fail to complete the study 
(even during a prerandomization screening period if a CRF was initiated). If a subject withdraws 

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from the study, the reason must be noted on the CRF. If a subject is withdrawn from the study 
because of a treatment-limiting adverse event, thorough efforts should be made to clearly 
document the outcome.
10.1.7.
Drug Accountability
The investigator or designee (i.e., pharmacist) is responsible for ensuring adequate accountability 
of all used and unused investigational medicinal product, and comparators. This includes 
acknowledgment of receipt of each shipment of study product (quantity and condition), subject 
dispensing records, and returned or destroyed study product. Dispensing records will document 
quantities received from Gilead Sciences and quantities dispensed to subjects, including lot 
number, date dispensed, subject identifier number, subject initials, and the initials of the person 
dispensing the medication.
At study initiation, the monitor will evaluate the site’s standard operating procedure for 
investigational medicinal product disposal/destruction in order to ensure that it complies with 
Gilead Sciences requirements. Drug may be returned or destroyed on an ongoing basis during the 
study if appropriate. At the end of the study, following final drug inventory reconciliation by the 
monitor, the study site will dispose of and/or destroy all unused investigational medicinal 
product supplies, including empty containers, according to these procedures. If the site cannot 
meet Gilead Sciences’ requirements for disposal, arrangements will be made between the site 
and Gilead Sciences or its representative for destruction or return of unused investigational 
medicinal product supplies.
All drug supplies and associated documentation will be periodically reviewed and verified by the 
study monitor over the course of the study.
10.1.8.
Inspections
The investigator should understand that source documents for this trial should be made available 
to appropriately qualified personnel from Gilead Sciences or its representatives, to IRBs or IECs, 
or to regulatory authority or health authority inspectors.
10.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
10.2.
Sponsor Responsibilities
10.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead Sciences. All protocol modifications must be submitted to the IRB, IEC, or 
competent authorities in accordance with local requirements. Approval must be obtained before 
changes can be implemented.

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10.2.2.
Study Report and Publications
A clinical study report will be prepared and provided to the regulatory agency(ies). 
Gilead Sciences 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.
After conclusion of the study and without prior written approval from Gilead Sciences, 
investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after the following conditions have been met:

the results of the study in their entirety have been publicly disclosed by or with the consent of 
Gilead Sciences in an abstract, manuscript, or presentation form; or

the study has been completed at all study sites for at least 2 years.
No such communication, presentation, or publication will include Gilead Sciences’ confidential 
information (see Section 10.1.4).
The investigator will submit any proposed publication or presentation along with the respective 
scientific journal or presentation forum at least 30 days before submission of the publication or 
presentation. The investigator will comply with Gilead Sciences’ request to delete references to 
its confidential information (other than the study results) in any paper or presentation and agrees 
to withhold publication or presentation for an additional 60 days in order to obtain patent 
protection if deemed necessary.
10.3.
Joint Investigator/Sponsor Responsibilities
10.3.1.
Access to Information for Monitoring
In accordance with ICH Good Clinical Practice (ICH GCP) guidelines, the study monitor must 
have direct access to the investigator’s source documentation in order to verify the data recorded 
in the CRFs for consistency.
The monitor is responsible for routine review of the CRFs 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 CRFs. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected in the course of these monitoring visits are resolved.
10.3.2.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead Sciences 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 Sciences medical monitor immediately. The investigator 
agrees to provide to representatives of a regulatory agency or Gilead Sciences access to records, 
facilities, and personnel for the effective conduct of any inspection or audit.

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10.3.3.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead Sciences and the 
investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests.

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11.
REFERENCES
19705
Esteban JI, Sauleda S, Quer J. The changing epidemiology of hepatitis C virus 
infection in Europe. J Hepatol 2008;48 (1):148-62.
19799
Hu J, Doucette K, Hartling L, Tjosvold L, Robinson J. Treatment of hepatitis C in 
children: a systematic review. PLoS ONE 2010;5 (7):e11542.
19801
Mohan N, Gonzalez-Peralta RP, Fujisawa T, Chang MH, Heller S, Jara P, et al. 
Chronic hepatitis C virus infection in children. J Pediatr Gastroenterol Nutr 
2010;50 (2):123-31.
20273
Bortolotti F, Verucchi G, Camma C, Cabibbo G, Zancan L, Indolfi G, et al. Long-
term course of chronic hepatitis C in children: from viral clearance to end-stage 
liver disease. Gastroenterology 2008;134 (7):1900-7.
20282
Serranti D, Buonsenso D, Ceccarelli M, Gargiullo L, Ranno O, Valentini P. 
Pediatric hepatitis C infection: to treat or not to treat...what's the best for the 
child? European review for medical and pharmacological sciences 2011;15 
(9):1057-67.
20285
Wirth S. Current treatment options and response rates in children with chronic 
hepatitis C. World J Gastroenterol 2012;18 (2):99-104.
20286
Wirth S, Ribes-Koninckx C, Calzado MA, Bortolotti F, Zancan L, Jara P, et al. 
High sustained virologic response rates in children with chronic hepatitis C 
receiving peginterferon alfa-2b plus ribavirin. J Hepatol 2010;52 (4):501-7.
28583
Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, et al. Ledipasvir and 
sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 2014;370 
(20):1889-98.
28585
Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, et al. 
Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N 
Engl J Med 2014;370 (16):1483-93.
28587
Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, et al. 
Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N 
Engl J Med 2014;370 (20):1879-88.
29292
Gane E, Hyland RH, An D, Pang PS, Symonds WT, McHutchison JG, et al. 
Ledipasvir/Sofosbuvir Fixed-Dose Combination Is Safe and Effective in Difficult-
to-Treat Populations Including GT 3 Patients, Decompensated GT 1 Patients, and 
GT 1 Patients With Prior Sofosbuvir Experience [Oral Presentation 6]. 49th 
Annual Meeting of The European Association for the Study of the Liver (EASL); 
2014 April 9-13; London, UK. 

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12.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table
Appendix 3.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Appendix 4.
Tanner Stages
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements

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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 2, Open-Label, Multicenter, Muti-cohort Study to Investigate the Safety and 
Efficacy of Ledipasvir/Sofosbuvir in Adolescents and Children with Chronic 
HCV -infection 
GS-US-337-1116, Original Protocol, 08 October 2014 
This protocol has been approved by Gilead Sciences, Inc. The fo llowing signature documents 
this approval. 
pp0..---------------. 
'1? 1\TOO 
Bittoo Kanwar, MD (Printed) 
Medical Monitor 
0~ Ocin\xr 
Date 
loll( 
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 Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 76 
08 October 2014 

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Appendix 2.
Study Procedures Table
Appendix Table 1.
PK Lead-in: Screening and On-Treatment Study Visits
Screening
(-28 days)
On-treatment
Day 1b
Day 3
Day 10
(+ 3 days)
Clinical Assessments
Informed Consent / Assent
X
Determine Eligibility
X
X
Medical History
X j
Complete Physical Examination
X
X
Symptom-directed Physical Examination
X
X
Tanner Pubertal Stage Assessment
X
Vital Signsa
X
X
X
X
Bone Age Assessment
X
AEs and Concomitant Medications
X
X
X
X
Pregnancy Prevention Counselingf
X
LDV/SOF FDC Swallowability Assessment
X
Xh
Quality of Life Survey
Xi
Review of Study 
Medication Compliance
X
X
Study Drug Dispensingb
X
Subject Dosing Diary
X
X
X

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Screening
(-28 days)
On-treatment
Day 1b
Day 3
Day 10
(+ 3 days)
Laboratory Assessments
Hematology, Chemistry
X
X
X
X
Coagulation Tests
X
X
X
HCV RNA
X
X
X
X
Viral Sequencing c
X
X
X
Serum or Urine Pregnancy Testinge
X
X
X
Urinalysis
X
X
X
Urine Drug Screen
X
Intensive PK
X d
HCV Genotyping, IL28B
X
HCV antibody, HIV 1/2 antibody, HBs 
antigen, HAV antibody
X
HbA1c
X
TSH
X
Alpha fetoprotein
X
Alpha-1 anti-trypsin
X
a
Vital signs include blood pressure, pulse, respiratory rate and temperature, body weight, and height
b
Day 1 assessments must be performed prior to dosing
c
Plasma samples will be collected and stored for potential HCV sequencing and other virology studies
d
For Cohorts 1 and 2, plasma samples will be collected for PK analyses following dosing of study drugs on Day 10 at the following time points: 0 (predose), 0.5, 1, 2, 3, 4, 5,
8, and 12 hours post-dose. For Cohort 3, plasma samples for PK analyses will be collected at the following time points: 0 (predose), 0.5, 2, 4, 8, and 12 hours post-dose.
PPD

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e
Females of childbearing potential only. Serum pregnancy test performed at screening and for confirmation of positive urine pregnancy test. 
f
Including partner pregnancy prevention for male participants (all subjects ≥ 12 years of age and subjects < 12 years of age at the discretion of the Investigator based on 
subject’s pubertal status). 
g
h
Swallowability can occur at Day 1 if not completed during screening.
i
Quality of life survey will be completed by all subjects if a site is approved to use the survey. Subject is to review questionnaire with a parent/guardian and write/mark 
answers directly onto the questionnaire.
j
Parental height will be collected with medical history at Screening (if available) as stated in Section 6.2.1
PPD

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Appendix Table 2.
Treatment Phase: Screening and On-Treatment Study Visits
Screeningc
(-28 days)
Day 1c
Visit identified by on-treatment study week
1c
2
4
8
12
Early 
Termination
Clinical Assessments
Informed Consent / Assent
X
Determine Eligibility
X
X
Medical History
Xi
Complete Physical Examination
X
X
X
X
Symptom-Directed Physical Examination
X
X
X
X
Tanner Pubertal Stage Assessment
X
X
X
Vital Signsa
X
X
X
X
X
X
X
X
Bone Age Assessment
X
AEs and Concomitant Medications
X
X
X
X
X
X
X
X
Pregnancy Prevention Counseling g
X
X
X
LDV/SOF FDC Swallowability Assessment
X
Xh
Quality of Life Survey e
X
X
X
Review of Study Medication Compliance
X
X
X
X
Study Drug Dispensingb
X
X
X
Laboratory Assessments
Hematology, Chemistry, Coagulation
X
X
X
X
X
X
X
X
HCV RNA
X
X
X
X
X
X
X
X

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Screeningc
(-28 days)
Day 1c
Visit identified by on-treatment study week
1c
2
4
8
12
Early 
Termination
Viral Sequencing d
X
X
X
X
X
X
X
Serum or Urine Pregnancy Testing
X
X
X
X
X
X
Single PK
X
X
X
X
X
X
Urinalysis
X
X
Urine Drug Test
X
HCV Genotyping, IL28B
X
HCV antibody, HIV 1/2 antibody, HBs antigen, 
HAV antibody
X
HbA1c
X
TSH
X
X
X
Alpha fetoprotein, Alpha-1 anti-trypsin
X
a
Vital signs include blood pressure, pulse, respiratory rate and temperature, and body weight and height
b
The IWRS will provide direction on the specifics of each subject’s study drug dispensing.
c
Subjects rolling over from PK Lead-in will not be required to repeat screening, Day 1 or Week 1 visits during the on Treatment Phase  
d
Plasma samples will be collected and stored for potential HCV sequencing and other virology studies
e
Quality of life survey will be completed at Day 1, Week 12, and Early Termination if a site is approved to use the survey. Subject is to review questionnaire with a 
parent/guardian and write/mark answers directly onto the questionnaire.
f
g
Including partner pregnancy prevention for male participants (all subjects ≥ 12 years of age and subjects < 12 years of age at the discretion of the Investigator based on 
subject’s pubertal status).
h
Swallowability can occur at Day 1 if not completed during screening.
i
Parental height will be collected with medical history at Screening (if available) as stated in Section 6.2.1
PPD
PPD

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Appendix Table 3.
Treatment Phase: Post Treatment Visits Following Primary Study
4 Weeks Post Treatment
12 Weeks Post Treatment
24 Weeks Post Treatment
Clinical Assessments
Vital Signs, Body weight and Height
X
X
X
Symptom-directed Physical Exam
X
X
X
AEs
X
Xc
Xc
Concomitant Medications
X
Quality of Life Survey a
X
X
Tanner Pubertal Stage Assessment 
X
X
Bone Age Assessment
X
Pregnancy Prevention Counselingd
X
X
Laboratory Assessments
Hematology, Chemistry
X
X
HCV RNA
X
X
X
Viral Sequencing b
X
X
X
Urine Pregnancy Test
X
X
a
Quality of life survey will be completed by all subjects at 12-Week and 24-Week Post Treatment visits if a site is approved to use the survey.  Subject is to review 
questionnaire with a parent/guardian and write/mark answers directly onto the questionnaire.
b
Plasma samples will be collected and stored for potential HCV sequencing and other virology studies
c
At Post Treatment Week 12 and 24, only SAEs will be captured
d
Including partner pregnancy prevention for male participants (all subjects ≥ 12 years of age and subjects < 12 years of age at the discretion of the Investigator based on 
subject’s pubertal status).

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Appendix 3.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Version: 18June2012
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 57 Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 57 Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease from Baseline
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease from Baseline
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L

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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Neutrophil Count 
(ANC)
Adult and Pediatric, 7 Days
1000 to 1300/mm3
750 to 1000/mm3
500 to 750/mm3
500/mm3
1.00 to 1.30 GI/L
0.75 to 1.00 GI/L
0.50 to 0.75 GI/L
0.50 GI/L
Infant, 2 – 7 Days
1250 to 1500/mm3
1.25 to 1.50 GI/L
1000 to 1250/mm3
1.00 to < 1.25 GI/L
750 to 1000/mm3
0.75 to < 1.00 GI/L
750/mm3
< 0.75 GI/L
Infant, 1 Day
4000 to 5000/mm3
4.00 to 5.00 GI/L
3000 to 4000/mm3
3.00 to < 4.00 GI/L
1500 to 3000/mm3
1.50 to < 3.00 GI/L
1500/mm3
< 1.50 GI/L
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L

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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0% 

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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 to <LLN mEq/L
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 to <LLN mmol/L
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
146  to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
146  to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
3.0 to 3.4 mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Hyperkalemia 
5.6 to 6.0 mEq/L
6.0 to 6.5 mEq/L
6.5 to 7.0 mEq/L
7.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mmol/L
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
40 to 55 mg/dL
30 to 40 mg/dL
30 mg/dL
3.03 to 3.58 mmol/L
2.20 to 3.03 mmol/L
1.64 to 2.20 mmol/L
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L
Hyperglycemia, Nonfasting 
116 to 160 mg/dL
160 to 250 mg/dL
250 to 500 mg/dL
500 mg/dL
6.42 to 8.91 mmol/L
8.91 to 13.90 mmol/L
13.90 to 27.79 mmol/L
27.79 mmol/L
Hyperglycemia, Fasting
110 to 125 mg/dL
6.08 to 6.96 mmol/L
>125 to 250 mg/dL
>6.96 to 13.90 mmol/L
>250 to 500 mg/dL
>13.90 to 27.79 mmol/L
>500 mg/dL
>27.79 mmol/L

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypocalcemia 
(corrected for albumin if 
appropriate*)
Adult and Pediatric
7 Days
7.8 to 8.4  mg/dL
7.0 to 7.8 mg/dL
6.1 to 7.0 mg/dL
6.1 mg/dL
1.94 to 2.10 mmol/L
1.74 to 1.94 mmol/L
1.51 to 1.74 mmol/L
1.51 mmol/L
Infant, 7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88  mmol/L
6.0 to 6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to 6.0 mg/dL
1.36 to < 1.49 mmol/L 
5.5 mg/dL
< 1.36 mmol/L
Hypercalcemia (corrected 
for albumin if appropriate*)
Adult and Pediatric 
7 Days
>ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
>ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10  mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23  mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38  mmol/L
13.5 mg/dL
> 3.38 mmol/L
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L
Hypercalcemia (ionized)
ULN to 6.0 mg/dL
6.0 to 6.5 mg/dL
6.5 to 7.0 mg/dL
7.0 mg/dL
ULN to 1.50 mmol/L
1.50 to 1.63 mmol/L
1.63 to 1.75 mmol/L
1.75 mmol/L

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 88
08 October 2014
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypomagnesemia
1.40 to  <LLN mg/dL
1.2 to <LLN mEq/L
1.04 to 1.40 mg/dL
0.9 to   1.2 mEq/L
0.67 to 1.04 mg/dL
0.6 to 0.9 mEq/L
0.67 mg/dL
0.6 mEq/L
0.58 to <LLN mmol/L
0.43 to 0.58 mmol/L
0.28 to 0.43 mmol/L
0.28 mmol/L
Hypophosphatemia
Adult and Pediatric
14 Years
2.0 to < LLN mg/dL
1.5 to 2.0 mg/dL
1.0 to 1.5 mg/dL
1.0 mg/dL
0.63  to LLN mmol/L
0.47 to 0.63 mmol/L
0.31 to 0.47 mmol/L
0.31 mmol/L
Pediatric 1 Year–14 Years 
3.0 to 3.5 mg/dL
0.96 to 1.14 mmol/L
2.5 to 3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Pediatric 1 Year
3.5 to 4.5 mg/dL
1.12 to 1.46 mmol/L
2.5 to 3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Hyperbilirubinemia 
Adult and Pediatric 
> 14 Days
1.0 to 1.5 ULN 
1.5 to 2.5 ULN
2.5 to 5.0 ULN 
5.0 ULN 
Infant, 14 Days
(non-hemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 to 30.0 mg/dL
> 428 to 513 μmol/L
30.0 mg/dL
> 513 μmol/L

LDV/SOF FDC
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Gilead Sciences, Inc
Amendment 1.0
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08 October 2014
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Infant, 14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 mg/dL
> 428 μmol/L
Blood Urea Nitrogen
1.25 to 2.50 ULN 
2.50 to 5.00 ULN 
5.00 to 10.00 ULN 
10.00 ULN
Hyperuricemia
>ULN to 10.0 mg/dL 
10.0 to 12.0 mg/dL 
12.0 to 15.0 mg/dL 
15.0 mg/dL
>ULN to 597 μmol/L
597 to 716 μmol/L
716 to 895 μmol/L
895 μmol/L
Hypouricemia
1.5 mg/dL to LLN
1.0 to 1.5 mg/dL
0.5 to 1.0 mg/dL
0.5 mg/dL
87 μmol/L to LLN
57 to 87 μmol/L
27 to 57 μmol/L
27 μmol/L
Creatinine 
1.50 to 2.00 mg/dL
2.00 to 3.00 mg/dL
3.00 to 6.00 mg/dL 
6.00 mg/dL
133 to 177 μmol/L
177 to 265 μmol/L
265 to 530 μmol/L
530 μmol/L
Bicarbonate
16.0 mEq/L to LLN 
11.0 to 16.0 mEq/L
8.0 to 11.0 mEq/L
8.0 mEq/L
16.0 mmol/L to LLN
11.0 to 16.0 mmol/L
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
NA
500 to 750 mg/dL
750 to 1200 mg/dL
1200 mg/dL
5.64–8.47 mmol/L
8.47–13.55 mmol/L
13.55 mmol/L
LDL
(Fasting)
130 to 160 mg/dL
>160 to 190 mg/dL
> 190 mg/dL
NA
3.35 to 4.15 mmol/L
>4.15 to 4.92 mmol/L
>4.92 mmol/L
Pediatric >2 to <18 years
110 to 130 mg/dL
>130 to 190 mg/dL
> 190 mg/dL
NA
2.84 to 3.37 mmol/L
>3.37 to  4.92 mmol/L
>4.92 mmol/L

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 90
08 October 2014
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypercholesterolemia
(Fasting)
200 to 239 mg/dL
239 to 300 mg/dL
300 mg/dL
NA
5.16 to 6.19 mmol/L
6.19 to 7.77 mmol/L
7.77 mmol/L
Pediatric 18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
199 to 300 mg/dL
5.15 to 7.77 mmol/L
300 mg/dL
7.77 mmol/L
NA
Creatine Kinase
3.0 to 6.0 ULN
6.0 to 10.0 ULN
10.0 to 20.0 ULN
20.0 ULN
*
Calcium should be corrected for albumin if albumin is < 4.0 g/dL

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
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ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
ALT (SGPT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
GGT
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Alkaline Phosphatase 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Total Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Pancreatic Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Lipase 
1.0 to 1.5 ULN
1.5 to 3.0 ULN
3.0 to 5.0 ULN
5.0 ULN
Albumin
3.0 g/dL to LLN
30 g/L to LLN
2.0 to 3.0 g/dL
20 to 30 g/L
2.0 g/dL
20 g/L
NA

LDV/SOF FDC
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Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
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08 October 2014
URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Hematuria (Dipstick) 
1
2
3-4+
NA
Hematuria (Quantitative) 
See Note below
                              Females
>ULN - 10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
                              Males
6-10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
Proteinuria (Dipstick)
1
2–3
4
NA
Proteinuria, 24 Hour Collection
Adult and Pediatric 
10 Years
200 to 999 mg/24 h
>999 to 1999 mg/24 h
>1999 to 3500 mg/24 h
3500 mg/24 h
Pediatric 3 Mo to 
< 10 Years
201 to 499 mg/m2/24 h
>499 to 799 mg/m2/24 h
>799 to 1000 mg/m2/24 h
1000 mg/ m2/24 h
Glycosuria (Dipstick)
1+
2-3
4
NA
Notes: 
Toxicity grades for Quantitative and Dipstick Hematuria will be assigned by Covance Laboratory, however for other laboratories, toxicity grades will only be assigned to Dipstick 
Hematuria.
With the exception of lipid tests, any graded laboratory test with a result that is between the LLN and ULN should be assigned Grade 0.
If the severity of a clinical AE could fall under either one of two grades (e.g., the severity of an AE could be either Grade 2 or Grade 3), select the higher of the two grades for the 
AE.

LDV/SOF FDC
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Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
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08 October 2014
CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Cardiac Arrhythmia (general)
(By ECG or physical exam)
Asymptomatic AND No 
intervention indicated
Asymptomatic AND Non-
urgent medical intervention 
indicated
Symptomatic, non-life-
threatening AND Non-
urgent medical intervention 
indicated 
Life-threatening arrhythmia 
OR Urgent intervention 
indicated
Cardiac-ischemia/Infarction
NA
NA
Symptomatic ischemia 
(stable angina) OR Testing 
consistent with ischemia 
Unstable angina OR Acute 
myocardial infarction
Hemorrhage (significant acute 
blood loss)
NA
Symptomatic AND No 
transfusion indicated
Symptomatic AND 
Transfusion of 2 units 
packed RBCs (for children 
10 cc/kg) indicated 
Life-threatening hypotension 
OR Transfusion of 2 units 
packed RBCs indicated (for 
children 10 cc/kg) indicated
Hypertension (with repeat 
testing at same visit)
140–159 mmHg systolic 
OR 
90–99 mmHg diastolic
159–179 mmHg systolic 
OR 
99–109 mmHg diastolic
179 mmHg systolic 
OR 
109 mmHg diastolic
Life-threatening consequences 
(eg, malignant hypertension) 
OR Hospitalization (other than 
ER visit) indicated
Pediatric 17 Years (with 
repeat testing at same visit)
NA
91st–94th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic)
≥95th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic)
Life-threatening consequences 
(eg, malignant hypertension) 
OR Hospitalization indicated 
(other than emergency room 
visit)
Hypotension
NA
Symptomatic, corrected with 
oral fluid replacement
Symptomatic, IV fluids 
indicated
Shock requiring use of 
vasopressors or mechanical 
assistance to maintain blood 
pressure
Pericardial Effusion
Asymptomatic, small 
effusion requiring no 
intervention
Asymptomatic, moderate or 
larger effusion requiring no 
intervention
Effusion with non-life-
threatening physiologic 
consequences OR Effusion 
with nonurgent intervention 
indicated
Life-threatening consequences 
(eg, tamponade) OR Urgent 
intervention indicated

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CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Prolonged PR Interval
PR interval 
0.21 to 0.25 sec
PR interval
0.25 sec
Type II 2nd degree AV 
block OR Ventricular pause 
3.0 sec
Complete AV block 
Pediatric 16 Years
1st degree AV block
(PR > normal for age and 
rate)
Type I 2nd degree AV block 
Type II 2nd degree AV 
block 
Complete AV block
Prolonged QTc
Asymptomatic, QTc interval 
0.45 to 0.47 sec OR Increase 
interval 0.03 sec above 
baseline
Asymptomatic, QTc interval 
0.48 to 0.49 sec OR Increase 
in interval 0.03 to 0.05 sec 
above baseline
Asymptomatic, QTc interval 
0.50 sec OR Increase in 
interval 0.06 sec above 
baseline
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Pediatric 16 Years
Asymptomatic, QTc interval 
0.450 to 0.464 sec 
Asymptomatic, QTc interval 
0.465 to 0.479 sec 
Asymptomatic, QTc interval 
0.480 sec 
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Thrombosis/Embolism
NA
Deep vein thrombosis AND 
No intervention indicated (eg, 
anticoagulation, lysis filter, 
invasive procedure) 
Deep vein thrombosis AND 
Intervention indicated (eg, 
anticoagulation, lysis filter, 
invasive procedure) 
Embolic event (eg, pulmonary 
embolism, life-threatening 
thrombus) 
Vasovagal Episode (associated 
with a procedure of any kind)
Present without loss of 
consciousness 
Present with transient loss of 
consciousness
NA 
NA
Ventricular Dysfunction 
(congestive heart failure, 
CHF)
NA
Asymptomatic diagnostic 
finding AND intervention 
indicated
New onset with symptoms 
OR Worsening symptomatic 
CHF
Life-threatening CHF

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RESPIRATORY
Grade 1
Grade 2
Grade 3
Grade 4
Bronchospasm (acute)
FEV1 or peak flow reduced to 
70% to 80%
FEV1 or peak flow 50% to 69%
FEV1 or peak flow 25% to 
49% 
Cyanosis OR FEV1 or peak flow 
25% OR Intubation
Dyspnea or Respiratory 
Distress
Dyspnea on exertion with no 
or minimal interference with 
usual social & functional 
activities 
Dyspnea on exertion causing 
greater than minimal interference 
with usual social & functional 
activities 
Dyspnea at rest causing 
inability to perform usual 
social & functional activities 
Respiratory failure with 
ventilatory support indicated
Pediatric 14 Years
Wheezing OR minimal 
increase in respiratory rate for 
age
Nasal flaring OR Intercostal 
retractions OR Pulse oximetry 
90% to 95%
Dyspnea at rest causing 
inability to perform usual 
social & functional activities 
OR Pulse oximetry 90%
Respiratory failure with 
ventilatory support indicated
OCULAR/VISUAL
Grade 1
Grade 2
Grade 3
Grade 4
Uveitis
Asymptomatic but detectable 
on exam
Symptomatic anterior uveitis OR 
Medical intervention indicated
Posterior or pan-uveitis OR 
Operative intervention 
indicated
Disabling visual loss in affected 
eye(s) 
Visual Changes (from 
baseline)
Visual changes causing no or 
minimal interference with 
usual social & functional 
activities
Visual changes causing greater 
than minimal interference with 
usual social & functional 
activities
Visual changes causing 
inability to perform usual 
social & functional activities
Disabling visual loss in affected 
eye(s)

LDV/SOF FDC
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Gilead Sciences, Inc
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SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Alopecia
Thinning detectable by 
study participant or  
caregiver (for disabled 
adults)
Thinning or patchy hair loss 
detectable by health care 
provider
Complete hair loss
NA
Cutaneous Reaction – Rash
Localized macular rash 
Diffuse macular, 
maculopapular, or 
morbilliform rash OR Target 
lesions 
Diffuse macular, 
maculopapular, or morbilliform 
rash with vesicles or limited 
number of bullae OR 
Superficial ulcerations of 
mucous membrane limited to 
one site
Extensive or generalized 
bullous lesions OR 
Stevens-Johnson syndrome 
OR Ulceration of mucous 
membrane involving two 
or more distinct mucosal 
sites OR Toxic epidermal 
necrolysis (TEN)
Hyperpigmentation
Slight or localized
Marked or generalized
NA
NA
Hypopigmentation
Slight or localized 
Marked or generalized
NA
NA
Pruritis (itching – no skin 
lesions) 
(See also Injection Site 
Reactions: Pruritis associated 
with injection)
Itching causing no or 
minimal interference with 
usual social & functional 
activities
Itching causing greater than 
minimal interference with 
usual social & functional 
activities
Itching causing inability to 
perform usual social & 
functional activities 
NA

LDV/SOF FDC
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Final
Gilead Sciences, Inc
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GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Anorexia
Loss of appetite without 
decreased oral intake
Loss of appetite associated with 
decreased oral intake without 
significant weight loss 
Loss of appetite associated 
with significant weight loss 
Life-threatening consequences 
OR Aggressive intervention 
indicated [eg, tube feeding or 
total parenteral nutrition]
Ascites
Asymptomatic
Symptomatic AND Intervention 
indicated (eg, diuretics or 
therapeutic paracentesis)
Symptomatic despite 
intervention
Life-threatening consequences
Cholecystitis
NA
Symptomatic AND Medical 
intervention indicated
Radiologic, endoscopic, or 
operative intervention 
indicated
Life-threatening consequences 
(eg, sepsis or perforation) 
Constipation 
NA
Persistent constipation requiring 
regular use of dietary 
modifications, laxatives, or 
enemas 
Obstipation with manual 
evacuation indicated
Life-threatening consequences 
(eg, obstruction)
Diarrhea 
Adult and Pediatric 
1 Year
Transient or intermittent 
episodes of unformed stools 
OR Increase of 3 stools 
over baseline/24 hr
Persistent episodes of unformed 
to watery stools OR Increase of 
4–6 stools over baseline per 
24 hrs. 
Bloody diarrhea OR Increase 
of 7 stools per 24-hour 
period OR IV fluid 
replacement indicated
Life-threatening consequences 
(eg, hypotensive shock)
Pediatric 1 Year
Liquid stools (more 
unformed than usual) but 
usual number of stools
Liquid stools with increased 
number of stools OR Mild 
dehydration
Liquid stools with moderate 
dehydration
Liquid stools resulting in 
severe dehydration with 
aggressive rehydration 
indicated OR Hypotensive 
shock
Dysphagia-Odynophagia 
Symptomatic but able to eat 
usual diet
Symptoms causing altered 
dietary intake without medical 
intervention indicated
Symptoms causing severely 
altered dietary intake with 
medical intervention indicated
Life-threatening reduction in 
oral intake

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GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Mucositis/Stomatitis 
(clinical exam)
See also Proctitis, 
Dysphagia-Odynophagia
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations 
Confluent pseudomembranes 
or ulcerations OR Mucosal 
bleeding with minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal bleeding 
OR Life-threatening 
consequences (eg, aspiration, 
choking)
Nausea 
Transient (24 hours) or 
intermittent nausea with no 
or minimal interference with 
oral intake
Persistent nausea resulting in 
decreased oral intake for 24–48 
hours
Persistent nausea resulting in 
minimal oral intake for 48 
hours OR Aggressive 
rehydration indicated (eg, 
IV fluids)
Life-threatening consequences 
(eg, hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not indicated 
(other than ER visit)
Symptomatic AND 
Hospitalization indicated 
(other than ER visit)
Life-threatening consequences 
(eg, sepsis, circulatory failure, 
hemorrhage)
Proctitis (functional-
symptomatic)
Also see Mucositis/ 
Stomatitis for Clinical 
Exam
Rectal discomfort AND No 
intervention indicated
Symptoms causing greater than 
minimal interference with usual 
social & functional activities OR 
Medical intervention indicated 
Symptoms causing inability to 
perform usual social/ 
functional activities OR 
Operative intervention 
indicated 
Life-threatening consequences 
(eg, perforation)
Vomiting
Transient or intermittent 
vomiting with no or 
minimal interference with 
oral intake
Frequent episodes of vomiting 
with no or mild dehydration
Persistent vomiting resulting 
in orthostatic hypotension OR 
Aggressive rehydration 
indicated
Life-threatening consequences 
(eg, hypotensive shock)

LDV/SOF FDC
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Final
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Amendment 1.0
CONFIDENTIAL
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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Alteration in Personality-
Behavior or in Mood (eg, 
agitation, anxiety, 
depression, mania, 
psychosis)
Alteration causing no or 
minimal interference with 
usual social & functional 
activities 
Alteration causing greater than 
minimal interference with 
usual social & functional 
activities 
Alteration causing inability to 
perform usual social & 
functional activities 
Behavior potentially harmful 
to self or others (eg, 
suicidal/homicidal ideation or 
attempt, acute psychosis) OR 
Causing inability to perform 
basic self-care functions
Altered Mental Status 
For Dementia, see Cognitive 
and Behavioral/Attentional 
Disturbance (including 
dementia and ADD)
Changes causing no or 
minimal interference with 
usual social & functional 
activities
Mild lethargy or somnolence 
causing greater than minimal 
interference with usual social 
& functional activities
Confusion, memory 
impairment, lethargy, or 
somnolence causing inability 
to perform usual social & 
functional activities
Delirium OR obtundation, OR 
coma
Ataxia 
Asymptomatic ataxia 
detectable on exam OR 
Minimal ataxia causing no 
or minimal interference with 
usual social & functional 
activities
Symptomatic ataxia causing 
greater than minimal 
interference with usual social 
& functional activities
Symptomatic ataxia causing 
inability to perform usual 
social & functional activities 
Disabling ataxia causing 
inability to perform basic self-
care functions
Cognitive and 
Behavioral/Attentional 
Disturbance (including 
dementia and Attention 
Deficit Disorder) 
Disability causing no or 
minimal interference with 
usual social & functional 
activities OR Specialized 
resources not indicated
Disability causing greater than 
minimal interference with 
usual social & functional 
activities OR Specialized 
resources on part-time basis 
indicated
Disability causing inability to 
perform usual social & 
functional activities OR 
Specialized resources on a 
full-time basis indicated
Disability causing inability to 
perform basic self-care 
functions OR 
Institutionalization indicated
CNS Ischemia
(acute)
NA
NA
Transient ischemic attack
Cerebral vascular accident 
(CVA, stroke) with 
neurological deficit 

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Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 100
08 October 2014
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Developmental delay –
Pediatric 16 Years
Mild developmental delay, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate 
for the setting 
Moderate developmental 
delay, either motor or 
cognitive, as determined by 
comparison with a 
developmental screening tool 
appropriate for the setting 
Severe developmental delay, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate for 
the setting 
Developmental regression, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate for 
the setting
Headache 
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference with 
usual social & functional 
activities
Symptoms causing inability to 
perform usual social & 
functional activities
Symptoms causing inability to 
perform basic self-care 
functions OR Hospitalization 
indicated (other than ER visit) 
OR Headache with significant 
impairment of alertness or
other neurologic function 
Insomnia
NA
Difficulty sleeping causing 
greater than minimal 
interference with usual 
social/functional activities
Difficulty sleeping causing 
inability to perform usual 
social & functional activities
Disabling insomnia causing 
inability to perform basic self-
care functions
Neuromuscular Weakness 
(including myopathy & 
neuropathy) 
Asymptomatic with 
decreased strength on exam 
OR Minimal muscle weak-
ness causing no or minimal 
interference with usual 
social & functional activities
Muscle weakness causing 
greater than minimal 
interference with usual social 
& functional activities
Muscle weakness causing 
inability to perform usual 
social & functional activities 
Disabling muscle weakness 
causing inability to perform 
basic self-care functions OR 
Respiratory muscle weakness 
impairing ventilation
Neurosensory Alteration 
(including paresthesia and 
painful neuropathy)
Asymptomatic with sensory 
alteration on exam or 
minimal paresthesia causing 
no or minimal interference 
with usual social &
functional activities 
Sensory alteration or 
paresthesia causing greater 
than minimal interference with 
usual social & functional 
activities 
Sensory alteration or 
paresthesia causing inability to 
perform usual social & 
functional activities
Disabling sensory alteration or 
paresthesia causing inability to 
perform basic self-care 
functions

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 101
08 October 2014
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Seizure: (new onset) 
NA
1 seizure 
2–4 seizures 
Seizures of any kind that are 
prolonged, repetitive (eg, 
status epilepticus), or difficult 
to control (eg, refractory 
epilepsy)
Seizure: (pre-existing) 
For Worsening of Existing 
Epilepsy the Grades Should 
Be Based on an Increase 
from Previous Level of 
Control to Any of These 
Levels
NA
Increased frequency of pre-
existing seizures (non-
repetitive) without change in 
seizure character OR 
infrequent breakthrough 
seizures while on stable meds 
in a previously controlled 
seizure disorder
Change in seizure character 
from baseline either in 
duration or quality (eg, 
severity or focality) 
Seizures of any kind that are 
prolonged, repetitive (eg, 
status epilepticus), or difficult 
to control (eg, refractory 
epilepsy)
Seizure 
– Pediatric 18 Years
Seizure, generalized onset 
with or without secondary 
generalization, lasting 
< 5 minutes with < 24 hours 
post ictal state
Seizure, generalized onset 
with or without secondary 
generalization, lasting 5–20 
minutes with 
< 24 hours post ictal state
Seizure, generalized onset 
with or without secondary 
generalization, lasting 
> 20 minutes 
Seizure, generalized onset 
with or without secondary 
generalization, requiring 
intubation and sedation
Syncope (not associated 
with a procedure)
NA
Present
NA
NA
Vertigo
Vertigo causing no or 
minimal interference with 
usual social & functional 
activities
Vertigo causing greater than 
minimal interference with 
usual social & functional 
activities 
Vertigo causing inability to 
perform usual social & 
functional activities
Disabling vertigo causing 
inability to perform basic self-
care functions

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Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 102
08 October 2014
MUSCULOSKELETAL
Grade 1
Grade 2
Grade 3
Grade 4
Arthralgia
See also Arthritis
Joint pain causing no or 
minimal interference with 
usual social & functional 
activities
Joint pain causing greater than 
minimal interference with usual 
social & functional activities
Joint pain causing inability 
to perform usual social & 
functional activities
Disabling joint pain causing 
inability to perform basic self-
care functions
Arthritis
See also Arthralgia
Stiffness or joint swelling 
causing no or minimal 
interference with usual 
social & functional activities
Stiffness or joint swelling causing 
greater than minimal interference 
with usual social & functional 
activities
Stiffness or joint swelling 
causing inability to perform 
usual social & functional 
activities
Disabling joint stiffness or 
swelling causing inability to 
perform basic self-care 
functions
Bone Mineral Loss
BMD t-score or z-score
–2.5 to –1.0 
BMD t-score or z-score –2.5
Pathological fracture 
(including loss of vertebral 
height)
Pathologic fracture causing 
life-threatening consequences 
Pediatric 21 Years
BMD z-score 
–2.5 to –1.0
BMD z-score < –2.5
Pathological fracture 
(including loss of vertebral 
height)
Pathologic fracture causing 
life-threatening consequences 
Myalgia
(non-injection site)
Muscle pain causing no or 
minimal interference with 
usual social & functional 
activities
Muscle pain causing greater than 
minimal interference with usual 
social & functional activities
Muscle pain causing 
inability to perform usual 
social & functional activities
Disabling muscle pain causing 
inability to perform basic self-
care functions
Osteonecrosis
NA
Asymptomatic with radiographic 
findings AND No operative 
intervention indicated
Symptomatic bone pain with 
radiographic findings OR 
Operative intervention 
indicated
Disabling bone pain with 
radiographic findings causing 
inability to perform basic self-
care functions

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Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 103
08 October 2014
SYSTEMIC
Grade 1
Grade 2
Grade 3
Grade 4
Acute Systemic Allergic 
Reaction 
Localized urticaria 
(wheals) with no medical 
intervention indicated
Localized urticaria with medical 
intervention indicated OR Mild 
angioedema with no medical 
intervention indicated
Generalized urticaria OR 
Angioedema with medical 
intervention indicated OR 
Symptomatic mild 
bronchospasm
Acute anaphylaxis OR Life-
threatening bronchospasm OR 
laryngeal edema
Chills
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater than 
minimal interference with usual 
social & functional activities 
Symptoms causing inability to 
perform usual social & 
functional activities
NA
Fatigue
Malaise
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater than 
minimal interference with usual 
social & functional activities
Symptoms causing inability to 
perform usual social & 
functional activities
Incapacitating fatigue/malaise 
symptoms causing inability to 
perform basic self-care 
functions
Fever (nonaxillary)
37.7C to 38.6C
99.8F to 101.5F
38.7C to 39.3C
101.6F to 102.8F
39.4C to 40.5C
102.9F to 104.9F
40.5C 
104.9F
Pain- Indicate Body Site
See also Injection Site 
Pain, Headache, 
Arthralgia, and Myalgia
Pain causing no or 
minimal interference with 
usual social & functional 
activities
Pain causing greater than minimal 
interference with usual social & 
functional activities
Pain causing inability to 
perform usual social & 
functional activities
Disabling pain causing 
inability to perform basic 
self-care functions OR 
Hospitalization (other than ER 
visit) indicated
Unintentional Weight 
Loss
NA
5% to 9% loss in body weight from 
baseline
10% to 19% loss in body 
weight from baseline
20% loss in body weight 
from baseline OR  Aggressive 
intervention indicated [eg, 
tube feeding or total parenteral 
nutrition]

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 104
08 October 2014
INJECTION SITE REACTION
Grade 1
Grade 2
Grade 3
Grade 4
Injection Site Pain (pain 
without touching)
Or Tenderness (pain when 
area is touched) 
Pain/tenderness causing no 
or minimal limitation of use 
of limb
Pain/tenderness limiting use of 
limb OR Pain/tenderness 
causing greater than minimal 
interference with usual social 
& functional activities
Pain/tenderness causing 
inability to perform usual
social & functional activities
Pain/tenderness causing inability 
to perform basic self-care 
function OR Hospitalization 
(other than ER visit) indicated 
for management of 
pain/tenderness
Injection Site Reaction 
(Localized), 15 Years
Erythema OR Induration
of 5 5 cm to 9 9 cm (or 
2581 cm2)
Erythema OR Induration OR 
Edema 9 cm any diameter 
(or 81 cm2)
Ulceration OR Secondary 
infection OR Phlebitis OR 
Sterile abscess OR Drainage
Necrosis (involving dermis and 
deeper tissue)
Pediatric 15 Years
Erythema OR Induration 
OR Edema present but 
2.5 cm diameter
Erythema OR Induration 
OR Edema > 2.5 cm 
diameter but < 50% surface 
area of the extremity 
segment (eg, upper 
arm/thigh)
Erythema OR Induration 
OR Edema involving 
50% surface area of the 
extremity segment (eg, 
upper arm/thigh) OR 
Ulceration OR Secondary 
infection OR Phlebitis OR 
Sterile abscess OR 
Drainage
Necrosis (involving dermis and 
deeper tissue)
Pruritis Associated with 
Injection 
See also Skin: Pruritis 
(itching—no skin lesions)
Itching localized to injection 
site AND Relieved 
spontaneously or with 
48 h treatment 
Itching beyond the injection 
site but not generalized OR 
Itching localized to injection 
site requiring 48 h treatment 
Generalized itching causing 
inability to perform usual 
social & functional activities
NA

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 105
08 October 2014
ENDOCRINE/METABOLIC
Grade 1
Grade 2
Grade 3
Grade 4
Lipodystrophy (eg, back 
of neck, breasts, 
abdomen)
Detectable by study 
participant or caregiver 
(for young children and 
disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious 
changes on casual visual 
inspection
NA
Diabetes Mellitus
NA
New onset without need to initiate 
medication OR Modification of 
current meds to regain glucose 
control
New onset with initiation of 
indicated med OR Diabetes 
uncontrolled despite treatment 
modification
Life-threatening consequences 
(eg, ketoacidosis, 
hyperosmolar non-ketotic 
coma) 
Gynecomastia
Detectable by study 
participant or caregiver 
(for young children and 
disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious on 
casual visual inspection
NA
Hyperthyroidism 
Asymptomatic
Symptomatic causing greater than 
minimal interference with usual 
social & functional activities OR 
Thyroid suppression therapy 
indicated
Symptoms causing inability to 
perform usual social & 
functional activities OR 
Uncontrolled despite treatment 
modification 
Life-threatening consequences 
(eg, thyroid storm)
Hypothyroidism
Asymptomatic
Symptomatic causing greater than 
minimal interference with usual 
social & functional activities OR 
Thyroid replacement therapy 
indicated
Symptoms causing inability to 
perform usual social & 
functional activities OR 
Uncontrolled despite treatment 
modification 
Life-threatening consequences 
(eg, myxedema coma)
Lipoatrophy (eg, fat loss 
from the face, extremities, 
buttocks)
Detectable by study 
participant or caregiver 
(for young children and 
disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious on 
casual visual inspection
NA

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 106
08 October 2014
GENITOURINARY
Grade 1
Grade 2
Grade 3
Grade 4
Intermenstrual Bleeding 
(IMB)
Spotting observed by participant 
OR Minimal blood observed 
during clinical or colposcopic 
exam
Intermenstrual bleeding not 
greater in duration or amount 
than usual menstrual cycle
Intermenstrual bleeding greater 
in duration or amount than usual 
menstrual cycle
Hemorrhage with life-
threatening hypotension OR 
Operative intervention 
indicated
Urinary Tract 
obstruction (eg, stone)
NA
Signs or symptoms of urinary 
tract obstruction without 
hydronephrosis or renal 
dysfunction
Signs or symptoms of urinary 
tract obstruction with 
hydronephrosis or renal 
dysfunction
Obstruction causing life-
threatening consequences
INFECTION
Grade 1
Grade 2
Grade 3
Grade 4
Infection (any other 
than HIV infection)
Localized, no systemic antiμbial 
treatment indicated AND 
Symptoms causing no or 
minimal interference with usual 
social & functional activities
Systemic antiμbial treatment 
indicated OR Symptoms 
causing greater than minimal 
interference with usual social 
& functional activities
Systemic antiμbial treatment 
indicated AND Symptoms 
causing inability to perform 
usual social & functional 
activities OR Operative 
intervention (other than simple 
incision and drainage) indicated
Life-threatening 
consequences (eg, septic 
shock)
Basic Self-care Functions: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding.
Usual Social & Functional Activities: Adaptive tasks and desirable activities, such as going to work, shopping, cooking, use of transportation, pursuing a hobby, etc

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 107
08 October 2014
Appendix 4.
Tanner Stages
1. Pubic hair (male and female)
Tanner I
no pubic hair at all (prepubertal Dominic state)
Tanner II
small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females)
Tanner III
hair becomes more coarse and curly, and begins to extend laterally
Tanner IV
adult-like hair quality, extending across pubis but sparing medial thighs
Tanner V
hair extends to medial surface of the thighs
2. Genitals (male) (One standard deviation around mean age)
Tanner I
Testes, scrotum, and penis about same size and proportion as in early childhood
Tanner II
Enlargement of scrotum and testes; skin of scrotum reddens and changes in texture; little or no enlargement of penis (10.5-12.5)
Tanner III
Enlargement of penis, first mainly in length; further growth of testes and scrotum (11.5-14)
Tanner IV
Increased size of penis with growth in breadth and development of glans; further enlargement of testes and scrotum and increased darkening 
of scrotal skin (13.5-15)
Tanner V 
Genitalia adult in size and shape
3. Breasts (female)
Tanner I
no glandular tissue: areola follows the skin contours of the chest
Tanner II
breast bud forms, with small area of surrounding glandular tissue; areola begins to widen 
Tanner III
breast begins to become more elevated, and extends beyond the borders of the areola, which continues to widen but remains in contour with 
surrounding breast 
Tanner IV
increased breast size and elevation; areola and papilla form a secondary mound projecting from the contour of the surrounding breast
Tanner V 
breast reaches final adult size; areola returns to contour of the surrounding breast, with a projecting central papilla. 

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 108
08 October 2014
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1. Background
Non-clinical toxicity studies of LDV/SOF FDC demonstrated no adverse effect on fertility or 
embryo-fetal development. However, there are no clinical studies of LDV/SOF FDC in pregnant 
women. Please refer to the latest version of the investigator’s brochure for additional 
information.
2. Definition of Female of Childbearing Potential and Contraceptive Requirements for 
Female Subjects (and their male partners)
For the purpose of this trial, all post-menarchal females will be considered to be of childbearing 
potential, unless there is documentation of irreversible ovarian failure or surgical sterilization.
Post-menarchal females must have a negative serum pregnancy test at Screening and a negative 
urine pregnancy test on the Day 1 visit prior to randomization. They must also agree to one of 
the following from 3 weeks prior to Day 1 until 30 days after last dose of LDV/SOF FDC:

Complete abstinence from intercourse. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, post-ovulation methods) is not permitted.
Or

Consistent and correct use of 1 of the following methods of birth control listed below, in 
addition to a male partner who correctly uses a condom, from the date of Screening until 
30 days  after the last dose of LDV/SOF FDC:
— intrauterine device (IUD) with a failure rate of < 1% per year
— female barrier method: cervical cap or diaphragm with spermicidal agent
— tubal sterilization
— vasectomy in male partner
— implants of levonorgestrel
— injectable progesterone
— oral contraceptives (either combined or progesterone only)
— contraceptive vaginal ring 
— transdermal contraceptive patch

LDV/SOF FDC
Protocol GS-US-337-1116
Final
Gilead Sciences, Inc
Amendment 1.0
CONFIDENTIAL
Page 109
08 October 2014
3. Contraceptive Requirements for Male Subjects (and their female partners)
All male study participants must agree to consistently and correctly use a condom from Day 1
until 90 days after the last dose of LDV/SOF FDC. If their female partner is of childbearing 
potential (as defined above), their female partner must use 1 of the methods of birth control listed 
above from the date of Screening until 90 days after last dose of LDV/SOF FDC.
Male subjects must agree to refrain from sperm donation for at least 90 days after the last dose of 
LDV/SOF FDC.
4. Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days (90 days for partners of male subjects) of 
last LDV/SOF FDC dose. Subjects who become pregnant or who suspect that they are pregnant 
must report the information to the investigator and discontinue study drug immediately. Subjects 
whose partner has become pregnant or suspects she is pregnant must report the information to 
the investigator. 
Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome are outlined in 
Section 8.5.2.1.