Conditions: HIV-1 Infection
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 48
Healthy volunteers: no

Brief summary:
The primary objectives of this study are to evaluate the safety and tolerability of escalating, multiple doses of vesatolimod (formerly GS-9620) in HIV-1 infected virologically suppressed adults on antiretroviral therapy (ART) and to evaluate the virologic effect of vesatolimod as measured by changes in plasma HIV-1 RNA.

Detailed description:

Arms:
arm 1: Vesatolimod 1 mg for 71 days, while continuing their existing ARV regimen arm 2: Vesatolimod 2 mg for 71 days, while continuing their existing ARV regimen arm 3: Vesatolimod 4 mg for 71 days, while continuing their existing ARV regimen arm 4: Vesatolimod 6 mg for 127 days, while continuing their existing ARV regimen arm 5: Vesatolimod 8 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen arm 6: Vesatolimod 10 or 12 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen. Participants will receive 3 administrations of 10 mg, followed by 7 administrations of 12 mg (after review of 10 mg safety data) arm 7: Vesatolimod up to 12 mg for up to 127 days for up to 10 total doses administered following overnight fasting, while continuing their existing ARV regimen arm 8: Vesatolimod 6 mg for 127 days for up to 10 total doses administered with an acidic solution (cranberry juice), while continuing their existing ARV regimen arm 9: Vesatolimod up to 12 mg for 127 days for up to 10 total doses administered following a moderate-fat meal, after the review of the data from the highest tolerated fasted dose cohort while continuing their existing ARV regimen arm 10: Placebo to match vesatolimod for 71 or 127 days, while continuing their existing ARV regimen

Interventions: intervention 1: Vesatolimod intervention 2: Placebo intervention 3: ARV regimen
Intervention descriptions: intervention 1: Tablet(s) administered orally once every 2 weeks intervention 2: Tablet(s) administered orally once every 2 weeks intervention 3: Participants' current ARV regimen must be used in accordance with their prescribing information and may include the following: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), raltegravir, dolutegravir, rilpivirine, and maraviroc.

Protocol document:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 1b, Randomized, Blinded, Placebo-Controlled 
Dose-Escalation Study of the Safety and Biological Activity of 
GS-9620 in HIV-1 Infected, Virologically Suppressed Adults
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov Identifier:
122452
Not Applicable
NCT02858401
Indication:
HIV-1 Infection
Protocol ID:
GS-US-382-1450
Clinical Program Manager:
Name:
Telephone:
Fax:
Gilead Medical Monitor:
Name:
Telephone:
Fax:
Mobile:
Gilead Study Director:
Name:
Telephone:
Fax:
Mobile:
Protocol Version/Date:
Amendment 7:
16 January 2019
Amendment 6:
07 June 2018
Amendment 5:
18 October 2017
Amendment 4:
13 October 2016
Amendment 3:
29 June 2015
Amendment 2:
15 December 2014
Amendment 1:
14 November 2014
Original:
16 September 2014
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or under
control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, potential 
investigator, or consultant, for review by you, your staff, and an applicable Institutional Review Board or 
Independent Ethics Committee. The information is only to be used by you in connection with authorized 
clinical studies of the investigational drug described in the protocol. You will not disclose any of the 
information to others without written authorization from Gilead Sciences, Inc., except to the extent 
necessary to obtain informed consent from those persons to whom the drug may be administered.
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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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....................................................................19
1.
INTRODUCTION ..............................................................................................................................................23
1.1.
Background ............................................................................................................................................23
1.2.
GS-9620 .................................................................................................................................................24
1.2.1.
General Information .............................................................................................................24
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................25
1.2.3.
Clinical Trials of GS-9620 ...................................................................................................27
1.3.
Rationale for This Study ........................................................................................................................31
1.4.
Rationale for Dose Selection/Dosing Interval........................................................................................32
1.5.
Rationale for Biomarker Testing............................................................................................................33
1.6.
Compliance ............................................................................................................................................34
2.
OBJECTIVES.....................................................................................................................................................35
3.
STUDY DESIGN................................................................................................................................................36
3.1.
Endpoints ...............................................................................................................................................36
3.2.
Study Design..........................................................................................................................................36
3.3.
Study Treatments ...................................................................................................................................38
3.4.
Duration of Treatment............................................................................................................................39
4.
SUBJECT POPULATION..................................................................................................................................40
4.1.
Number of Subjects and Subject Selection ............................................................................................40
4.2.
Inclusion Criteria (All Cohorts) .............................................................................................................40
4.3.
Exclusion Criteria (All Cohorts) ............................................................................................................42
4.4.
Other Protocol Restrictions ....................................................................................................................43
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................44
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................44
5.1.1.
Procedures for Breaking Treatment Codes...........................................................................44
5.2.
Description and Handling of GS-9620 and Placebo to match................................................................45
5.2.1.
Formulation..........................................................................................................................45
5.2.2.
Packaging and Labeling .......................................................................................................45
5.3.
Dosage and Administration of GS-9620 ................................................................................................45
5.3.1.
Fasting and food/liquids Requirement..................................................................................45
5.3.3.
Storage and Handling...........................................................................................................47
5.4.
Prior and Concomitant Medications.......................................................................................................48
5.5.
Accountability for GS-9620...................................................................................................................50
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................50
6.
STUDY PROCEDURES ....................................................................................................................................51
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................51
6.2.
Pretreatment Assessments Screening Visit (all cohorts) ........................................................................51
6.2.2.
Pre-Baseline/Day -13 Assessments (all Cohorts).................................................................53
6.2.3.
Baseline/Day 1 Assessments (all Cohorts)...........................................................................54
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6.3.
Treatment Assessments (Cohorts 1 to 3)................................................................................................56
6.3.1.
Treatment Assessments on Non Dosing Days 3, 5, 11, 17, 19, 25, 31, 33, 
39, 45, 47, 53, 59, 61, 67, 73, 75 and 81 ..............................................................................56
6.3.2.
Treatment Assessments on Non Dosing Days 8, 22, 36, 50, 64 and 78 ...............................57
6.3.3.
Treatment Assessments on Dosing Days 15, 29, 43, 57 and 71...........................................57
6.4.
Treatment Assessments (Cohorts 4 to 9)................................................................................................59
6.4.1.
Treatment Assessments on Non Dosing Days 2, 58 and 128...............................................59
6.4.2.
Treatment Assessments on Non Dosing Days 3, 59 and 129...............................................60
6.4.3.
Treatment Assessments on Non Dosing Days 8, 22, 36, 50, 64, 78, 92, 
106, 120 and 134..................................................................................................................60
6.4.4.
Treatment Assessments on Dosing Days 15, 29, 43, 57, 71, 85, 99, 113 
and 127.................................................................................................................................61
6.4.5.
Treatment Assessments on Non Dosing Days 31, 45, 73, 87, 101 and 115 
(For Cohorts 5 to 9 only)......................................................................................................63
6.5.
Post-treatment Assessments ...................................................................................................................64
6.5.1.
End of Study Visit (all Cohorts)...........................................................................................64
6.5.2.
Early Study Drug Discontinuation Visit (all Cohorts) .........................................................65
6.6.
Criteria for Discontinuation of Study Treatment....................................................................................66
6.8.
Prolonged Viremia .................................................................................................................................67
6.8.1.
Management of Prolonged Viremia .....................................................................................67
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................68
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................68
7.1.1.
Adverse Events.....................................................................................................................68
7.1.2.
Serious Adverse Events........................................................................................................68
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................69
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................69
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................69
7.2.2.
Assessment of Severity ........................................................................................................70
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................70
7.4.
Gilead Reporting Requirements.............................................................................................................72
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events..........................................................................................................................72
7.6.
Toxicity Management ............................................................................................................................73
7.6.1.
Management of Dose-Limiting Toxicities (DLTs)...............................................................73
7.6.2.
Management of Other Toxicities..........................................................................................74
7.7.
Special Situations Reports......................................................................................................................75
7.7.1.
Definitions of Special Situations..........................................................................................75
7.7.2.
Instructions for Reporting Special Situations.......................................................................76
8.
STATISTICAL CONSIDERATIONS................................................................................................................78
8.1.
Analysis Objectives and Endpoints........................................................................................................78
8.1.1.
Analysis Objectives..............................................................................................................78
8.1.2.
Primary Endpoint .................................................................................................................78
8.1.3.
Secondary Endpoint .............................................................................................................79
8.1.4.
Other Endpoints of Interest ..................................................................................................79
8.1.5.
Exploratory Endpoints..........................................................................................................79
8.2.
Analysis Conventions.............................................................................................................................79
8.2.1.
Analysis Sets ........................................................................................................................79
8.3.
Data Handling Conventions ...................................................................................................................80
8.4.
Demographic Data and Baseline Characteristics ...................................................................................80
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8.5.
Efficacy Analysis ...................................................................................................................................81
8.5.1.
Primary Analysis..................................................................................................................81
8.5.2.
Secondary Analyses .............................................................................................................81
8.6.
Safety Analysis.......................................................................................................................................81
8.6.1.
Extent of Exposure...............................................................................................................81
8.6.2.
Adverse Events.....................................................................................................................81
8.6.3.
Laboratory Evaluations ........................................................................................................82
8.7.
Pharmacokinetic Analysis......................................................................................................................82
8.8.
Sample Size............................................................................................................................................83
8.9.
Safety Evaluation Committee.................................................................................................................83
8.10.
Analysis Schedule ..................................................................................................................................83
9.
RESPONSIBILITIES..........................................................................................................................................84
9.1.
Investigator Responsibilities ..................................................................................................................84
9.1.1.
Good Clinical Practice..........................................................................................................84
9.1.2.
Institutional Review Board (IRB) Review and Approval.....................................................84
9.1.3.
Informed Consent.................................................................................................................84
9.1.4.
Confidentiality......................................................................................................................85
9.1.5.
Study Files and Retention of Records ..................................................................................85
9.1.6.
Case Report Forms...............................................................................................................86
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................87
9.1.8.
Inspections............................................................................................................................87
9.1.9.
Protocol Compliance............................................................................................................87
9.2.
Sponsor Responsibilities ........................................................................................................................87
9.2.1.
Protocol Modifications.........................................................................................................87
9.2.2.
Study Report and Publications .............................................................................................87
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................88
9.3.1.
Payment Reporting...............................................................................................................88
9.3.2.
Access to Information for Monitoring..................................................................................88
9.3.3.
Access to Information for Auditing or Inspections ..............................................................89
9.3.4.
Study Discontinuation..........................................................................................................89
10.
REFERENCES ...................................................................................................................................................90
11.
APPENDICES ....................................................................................................................................................92
Appendix 1.
Investigator Signature Page....................................................................................................93
Appendix 2.
Study Procedures Table..........................................................................................................94
Appendix 3.
Management of Clinical and Laboratory Adverse Events....................................................105
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.............106
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................129
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................132


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LIST OF IN-TEXT TABLES
Table 1-1.
Estimated Margins of GS-9620 Following Oral Administration at the Highest 
Anticipated Human Dose .......................................................................................................27
Table 5-1.
Fasting and food/liquids Requirement....................................................................................46
Table 5-2.
Recommended Moderate-Fat Meal ........................................................................................47
Table 5-3.
Prohibited Concomitant Medications .....................................................................................49
LIST OF IN-TEXT FIGURES
Figure 3-1.
High-Level Study Schema......................................................................................................38
Figure 3-2.
Cohort 6 Visit Schema............................................................................................................38


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title:
A Phase 1b, Randomized, Blinded, Placebo-Controlled 
Dose-Escalation Study of the Safety and Biological Activity of 
GS-9620 in HIV-1 Infected, Virologically Suppressed Adults
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
122452
Not Applicable
NCT02858401
Study Centers Planned:
Multiple centers in North America
Objectives:
The primary objectives are:

To evaluate the safety and tolerability of escalating, 
multiple doses of GS-9620 in HIV-1 infected virologically 
suppressed adults on antiretroviral therapy (ART)

To evaluate the virologic effect of GS-9620 as measured by 
changes in plasma HIV-1 RNA
The secondary objectives are:

To evaluate the plasma pharmacokinetics (PK) of GS-9620

To evaluate the pharmacodynamics (PD) of GS-9620 as 
measured by changes in interferon-stimulated genes (ISGs)
and serum cytokines in whole blood compared to placebo

To evaluate effects of GS-9620 on whole blood immune cell 
activation (T cell, B cell, NK cell) 
The exploratory objectives are:
 
 
 
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Study Design:
This is a randomized, double-blinded, multi-cohort
dose-escalation study with dose cohorts: Cohort 1 (1 mg Dose), 
Cohort 2 (2 mg Dose), Cohort 3 (4 mg Dose), Cohort 4
(6 mg Dose), Cohort 5 (8 mg Dose), Cohort 6 
(three administrations of 10 mg Dose, followed by
seven administrations of 12 mg Dose; SEC review of the 10mg 
safety data will be required prior to dose escalating to 12mg), and 
optional Cohort 7
 
 
 
 
 
Two additional optional adaptive cohorts, Cohort 8 
 
and Cohort 9 
 
 
 
For each cohort, eight subjects will be randomized in a 6:2 ratio 
to receive GS-9620 or placebo. 
Subjects will receive a total of either 6 doses in Cohorts 1 to 3,
10 doses in Cohorts 4 to 6,
 
of their assigned study treatment administered once every 
other week. For all subjects in Cohort 6, Dose 4 (Day 43) will 
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occur after SEC review has been completed. If dose escalation is 
approved by the SEC, subjects in Cohort 6 will receive 12 mg of 
GS-9620 or placebo from Doses 4 to 10; if dose escalation is not 
approved by the SEC, subjects will continue receiving 10 mg of 
GS-9620 or placebo from Doses 4 to 10.
Enrollment will initially be opened for Cohort 1 only. A SEC will 
review study progress, safety and virology results of enrolled 
subjects. After all subjects in a cohort have received at least 
three doses (Cohorts 1 to 3, and 6) or five doses (Cohorts 4 
and 5), the SEC will review safety data from that cohort, 
including adverse events (AEs) and clinical laboratory results 
(including plasma HIV-1 RNA) before approving the next dose 
escalation. 
 
A cohort may be suspended if 
≥2 out of 6 subjects receiving GS-9620 experience one or more 
dose-limiting toxicities (DLTs) considered related to study drug.
Number of Subjects 
Planned:
Approximately up to 72 subjects total (6 GS-9620; 2 placebo per 
cohort)
Subjects who discontinue study participation before completion 
of dosing for reasons other than study treatment-related AEs may 
be replaced
Target Population:
HIV-1 infected male and non-pregnant, non-lactating female 
adults who have been virologically suppressed 
(HIV-1 RNA < 50 copies/mL) on ART for 
12 consecutive months prior to screening
Main Eligibility Criteria:

HIV-1 infection

Aged 18 years at Pre-Baseline/Day -13

On antiretroviral (ARV) treatment for
12 consecutive months prior to Pre-Baseline/Day -13
The following agents are allowed as part of the current 
ARV regimen: NRTIs, raltegravir, dolutegravir, 
rilpivirine, and maraviroc
The following agents are NOT allowed as part of the 
current ARV regimen: HIV protease inhibitors 
(including low dose ritonavir), cobicistat-containing 
regimens, elvitegravir, efavirenz, etravirine, and 
nevirapine
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A change in ARV regimen 45 days prior to 
Baseline/Day 1 for reasons other than virologic failure 
(eg, tolerability, simplification, drug-drug interaction 
profile) is allowed

Plasma HIV-1 RNA < 50 copies/mL at screening

Documented plasma HIV-1 RNA levels < 50 copies/mL 
(according to the local assay being used) for 12 months 
preceding the screening visit (measured at least twice using a 
licensed assay with a lower limit of quantitation of at least 
40 copies/mL) 
Unconfirmed virologic elevations of ≥50 copies/mL 
(transient detectable viremia, or “blip”) prior to screening 
are acceptable. (If the lower limit of detection of the local 
HIV-1 RNA assay is < 50 copies/mL, the plasma HIV-1 
RNA level cannot exceed 50 copies/mL on two 
consecutive HIV-1 RNA tests)
If ARV regimen is changed ≥ 45 days prior to 
Pre-Baseline/Day -13, plasma HIV-1 RNA <50 copies/mL 
at Pre-baseline/Day -13 visit is required.

No documented history of resistance to any components of the 
current ARV regimen

Availability of a fully active alternative ARV regimen, in the 
opinion of the Investigator, in the event of discontinuation of 
the current ARV regimen with development of resistance.

Hgb 11.5 g/dL (males) or 11 g/dL (females)

WBC 4000 cells/μL

Platelets 150,000/mL

ANC 1500 cells/μL

CD4 count 400 cells/μL

Albumin 3.9 g/dL

ALT and AST 2 × ULN

Estimated glomerular filtration rate 60 mL/min

No autoimmune disease(e.g. lupus erythematosus, rheumatoid 
arthritis, inflammatory bowel disease, sarcoidosis, moderate 
or severe psoriasis)

No evidence of current HBV infection
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
No evidence of current HCV infection
Positive anti-HCV antibody and negative HCV PCR 
results are acceptable

No documented history of pre-ART CD4 nadir < 200 cells/μL
Unknown pre-ART CD4 nadir is acceptable

No history of Class C AIDS-Defining Condition
No acute febrile illness within 35 days prior to 
Pre-Baseline/Day -13
Study Visits and 
Procedures:
Visit Schedule:
The main study phase consists of a screening period of up to 
35 days, a pre-treatment period of 14 Days 
(from Day -13 to Day 1), treatment period of 71 days (Cohorts 1 
to 3), 127 days (Cohorts 4 to 6), 
 and a follow-up period of 30 days after the last dose of study 
drug is taken. Enrolled subjects will undergo the following 
scheduled study visits: 
Cohort 1 to Cohort 3
Day -13 (Pre-Baseline)
Day 1 (Baseline/Dose 1), Day 3, Day 5, Day 8, Day 11
Day 15 (Dose 2), Day 17, Day 19, Day 22, Day 25
Day 29 (Dose 3), Day 31, Day 33, Day 36, Day 39
Day 43 (Dose 4), Day 45, Day 47, Day 50, Day 53
Day 57 (Dose 5), Day 59, Day 61, Day 64, Day 67
Day 71 (Dose 6), Day 73, Day 75, Day 78, Day 81
Day 101 (End of Study)
Cohort 4
Day -13 (Pre-Baseline)
Day 1 (Baseline/Dose 1), Day 2, Day 3, Day 8
Day 15 (Dose 2), Day 22
Day 29 (Dose 3), Day 36
Day 43 (Dose 4), Day 50
Day 57 (Dose 5), Day 58, Day 59, Day 64
Day 71 (Dose 6), Day 78
Day 85 (Dose 7), Day 92
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Day 99 (Dose 8), Day 106
Day 113 (Dose 9), Day 120
Day 127 (Dose 10), Day 128, Day 129, Day 134
Day 157 (End of Study)
Cohorts 5 to 9
Day -13 (Pre-Baseline)
Day 1 (Baseline/Dose 1), Day 2, Day 3, Day 8
Day 15 (Dose 2), Day 22
Day 29 (Dose 3), Day 31, Day 36
Day 43 (Dose 4), Day 45, Day 50
Day 57 (Dose 5), Day 58, Day 59, Day 64
Day 71 (Dose 6), Day 73, Day 78
Day 85 (Dose 7), Day 87, Day 92
Day 99 (Dose 8), Day 101, Day 106
Day 113 (Dose 9), Day 115, Day 120
Day 127 (Dose 10), Day 128, Day 129, Day 134
Day 157 (End of Study)
Subjects who prematurely discontinue study drug will be required 
to complete an Early Study Drug Discontinuation Visit within 
30 days after their last dose of study treatment.
The Pre-Baseline/Day -13 visit has an allowable window of 
± 3 days.

Visits scheduled for 2, 4, 7, or 10 days after a Dosing visit, 
except for Day 2, 3, 58, 59, 128 and 129 have an allowable 
window of ± 1 day.
The Day 101 and 157 visits have an allowable window of 
± 3 days.
Non-dosing visits may occur at the investigator site or at other 
location agreed by the subject and mobile nurse vendor.
Screening Procedures:
Screening procedures include: complete physical examination, 
vital signs, height, weight, medical history (including route and 
estimated duration of HIV infection, pre-ART viral set point, and 
complete ARV history), HIV-1 RNA, ARV trough PK, 
hematology, serum chemistry, serum pregnancy test, urinalysis, 
HBV and HCV serologies, eGFR, and electrocardiogram (ECG). 
Pre-ART CD4 nadir and historical genotype will be collected 
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In order to establish eligibility, Investigators may repeat screening 
procedures or laboratory assessments for subjects who have an 
acute illness or abnormal laboratory value that is expected to 
resolve without sequelae within the screening window.
On-Study Procedures:
Dosing:
For Cohorts 1 to 3, dosing visits will occur at Day 1, Day 15, 
Day 29, Day 43, Day 57, and Day 71. For Cohorts 4 to 9, dosing 
visits will occur at Day 1, Day 15, Day 29, Day 43, Day 57, 
Day 71, Day 85, Day 99, Day 113 and Day 127.
 
For Cohorts 1 to 4, subjects will fast for at least 
2 hours before dosing. For Cohorts 5 to 8, subjects will fast 
overnight (at least 8 hours) before dosing. 
 
The Investigator will verify the subject’s continued 
eligibility for dosing at post-Baseline dosing visits, including the 
absence of dose-limiting toxicities (DLTs) and (for females of 
childbearing potential) a negative urine pregnancy test, prior to 
dosing. All doses will be directly administered by blinded site 
staff. Subjects will fast for 2 hours after dosing for all cohorts. 
After Dose 1, subjects will remain on site for 12 hours after 
dosing for safety assessment and phlebotomy.
Safety:
Solicitation of AEs and concomitant medications and 
symptom-directed physical examination at every visit.
Hematology, serum chemistry, and urinalysis weekly for 
Cohorts 1 to 3. For Cohorts 4 to 9 these labs will be collected on 
dosing days, seven days post dose (starting from Dose 4), at end 
of study, and ESDD. For Cohorts 6 
 these labs will also be 
collected on Day 2 and two days post dose (starting from Dose 5).
 
Urine pregnancy test (for females of childbearing potential) prior 
to each dose.
Vital signs (blood pressure, pulse, respiration rate 
and temperature) at all dosing visits.
Subjects will be instructed to contact the site immediately if any 
flu-like symptoms are noted (eg, fatigue, pyrexia, chills, myalgia, 
joint pain or headache).
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Pharmacokinetics:
Plasma GS-9620 concentrations will be collected at the following 
time points for all cohorts:

Pre-dose (≤5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, 
and 12 hours post dose at Day 1; then one sample 48 hours 
post dose at Day 3

If the SEC approves the dose escalation to 12 mg in 
Cohort 6, starting from Dose 4 and onwards, plasma 
GS-9620 concentrations will also be collected on Day 43
(Dose 4): Pre-dose (≤5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 
8, 10, and 12 hours post dose; then one sample 48 hours 
post dose at Day 45
 
A single trough ARV PK sample will be collected at 
Pre-Baseline/Day -13 (Cohorts 1 to 3) or at Screening, Day 29, 
Day 57, Day 85 and Day 99 (Cohort 5), or at Screening, Day 57 
and Day 99 (Cohorts 6
 
The timing of the ARV 
trough collection is to be 20-24 hours following the subject’s 
previous QD regimen dose and before next ARV dose (and, for 
any subject on a regimen containing a BID component, the trough 
collection must also occur 8-12 hours following the subject’s 
previous dose of that BID component and before next ARV dose). 
These samples may be analyzed to assess interim ART adherence.
Pharmacodynamics:
Whole blood ISG mRNA panel: For Cohorts 1 to 3, immediately 
before and 2 days and 7 days after each dose of study drug, and at 
the end of the study (Day 101). For Cohorts 4 to 9, immediately 
before and 1 day, 2 days and 7 days after doses 1, 4 (only if 
Cohort 6 subjects receive 12 mg starting at Dose 4), 5 and 10.
 
TLR7 genotyping: at Pre-Baseline/Day -13
CCI CCI
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Virology:
Plasma HIV-1 RNA: at every visit except Pre-Baseline (Day -13).
Cell-associated HIV-1 RNA/DNA (CAVR/CAVD), and plasma 
HIV-1 RNA by Single Copy Assay (SCA) will be collected 
immediately before and two days post Doses 1, 4, 6 and at end of 
the study (Cohort 1 to 3); immediately before and two days post 
Doses 1, 5, 10 and at end of the study (Cohorts 4 to 9).
 
 
HIV-1 reservoir measurements: at Pre-Baseline/Day -13 and at 
the end of the study (Cohorts 4 to 9).
 
 
Immunology:
Peripheral blood immune cell numbers for T/B/NK/pDC/mDC 
including: CD4 and CD8 populations, CD4/CD8 ratio, CD4% and 
lymphocyte activation (T, B and NK cells) by flow cytometry will 
be collected immediately before and two days post Doses 1, 3, 
and 6 (Cohorts 1 to 3), and immediately before, one and two days 
post Doses 1, 5 and 10 (Cohorts 4 to 9). 
 
FoxP3+ Treg cells by flow cytometry will be collected
immediately before Doses 1, 3, and 6 (Cohorts 1 to 3), and 
immediately before Doses 1, 5 and 10 (Cohort 4 to 9). 
 
 
Changes in the levels of antiviral cytokines and inflammatory 
markers by chemiluminescence: immediately before and 2 days 
and 7 days after each dose, and at the end of the study (Cohorts 1 
to 3). For subjects in Cohorts 4 to 9, immediately before, 
post dose days 1, 2 and 7 after Doses 1, 4 (only if Cohort 6
subjects receive 12 mg at Dose 4), 5 and 10.
PBMC Intracellular cytokine staining (ICS) for Treg cells:
immediately before and 2 days after Doses 1 and 6 for subjects in 
Cohorts 1 to 3.
CCI
CCI
CCI
CCI
CCI


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HIV-specific T-cell responses by ELISPOT will be collected at 
Pre-Baseline/Day -13, immediately before Dose 6 and at the end 
of study for subjects in Cohorts 1 to 3. 
For subjects in Cohorts 4 to 9, HIV-specific polyfunctional T cell 
Intracellular Cytokine Staining (ICS) and HIV-specific T-cell 
responses by ELISPOT will be collected at Pre-Baseline/Day -13 
and at the end of the study.
 
Stool sample will be obtained for microbiome analysis. (Day 1 
and Day 157 for Cohorts 5 to 9).
 
 
 
 
 
 
 
Additional End of Study Procedures:
Symptom-directed physical examination, review of AEs and 
concomitant medications, weight, eGFR, hematology, serum 
chemistry, urinalysis, urine pregnancy test (for females of 
childbearing potential, if not performed within the previous 
30 days).
Early Study Drug Discontinuation Visit Procedures:
Symptom-directed physical examination, review of AEs and 
concomitant medications, weight, eGFR, HIV-1 RNA, 
hematology, serum chemistry, whole blood ISG mRNA panel, 
serum cytokine/soluble biomarker studies, urinalysis, urine 
pregnancy test.
Procedure Definitions and Specifications:
HIV-1 RNA will be performed by a licensed assay with a lower 
limit of quantitation of at least 20 copies/mL.
Hematology panel includes: complete blood count (CBC) with 
differential and platelets, CD4+ cell count, CD8+ cell count, 
CD4/CD8 ratio, and CD4%.
CCI
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Serum chemistry panel includes: alkaline phosphatase, AST, 
ALT, total and direct bilirubin, total protein, albumin, 
bicarbonate, BUN, calcium, chloride, creatinine, glucose, 
phosphate, magnesium, potassium, sodium, CPK, and uric acid.
Urinalysis includes dipstick. Serum and urine pregnancy tests
are performed only on female subjects of childbearing potential.
Phlebotomy volume limits will be maintained in accordance with 
American Red Cross blood donation guidelines, which limit 
blood donation to 473 mL every 56 days. Subjects will undergo 
periodic phlebotomy over a 149-day period and will provide no 
more than 473 mL every 56 days. Subjects will be prohibited 
from blood donation in excess of that required for clinical care 
within 30 days prior to screening and 30 days after study ends.
Study Treatment:
Investigational 
Medicinal Products:
GS-9620: 1 mg, 2 mg, 4 mg, 6 mg (administered as three 2 mg 
tablets), 8 mg (administered as two 4 mg tablets), 10 mg 
(administered as five 2 mg tablets), 12 mg (administered as
six 2 mg tablets, or three 4 mg tablets) dose administered orally 
once every other week. 
Reference Treatment:
Placebo-to-match GS-9620, administered orally once every other 
week. 
Duration of Treatment:
The treatment duration is 71 days (Cohorts 1 to 3), 127 days
(Cohorts 4 to 6), 
 
Other Treatment:
Subjects will continue their existing ARV regimen (as currently 
prescribed and supplied) for the duration of study participation.
Criteria for Evaluation:
Safety:
AEs and clinical laboratory tests will be collected at every visit 
and summarized through Day 101 or Day 157 (30 days after the 
last dose of GS-9620 or placebo).
The following are DLTs:

ALT elevation defined as:
ALT ≥10 × ULN OR
confirmed ALT elevation (i.e. grade shift or 2 × previous 
value) with evidence of worsened hepatic function 
(e.g. total bilirubin > 2 mg/dL above Baseline, serum 
albumin > 1 g/dL decrease from Baseline)

A confirmed ≥ Grade 3 AE considered by the investigator to 
be study drug-related
CCI


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
A confirmed ≥ Grade 3 lab abnormality considered by the 
investigator to be study drug-related and clinically significant

A persistent (≥ 72 hours) ≥Grade 2 flu-like symptom 
(eg pyrexia, fatigue, myalgia, arthralgia, headache, chills) 
considered by the investigator to be study drug-related

A post-dose increase in plasma HIV-1 RNA that fails to 
resolve to < 50 copies/mL within 10 days in Cohorts 1 to 3

A post-dose increase in plasma HIV-1 RNA that fails to 
resolve to < 200 copies/mL within 10 days in Cohorts 4 to 9
The Investigator will notify the SEC within 24 hours of any DLT. 
The SEC may unblind the treatment assignment for a subject 
experiencing a DLT.
Study drug dosing for a subject may be discontinued if the 
subject receives GS-9620 and experiences one or more DLTs 
considered to be related to study drug.
A Dose Cohort may be discontinued if ≥ 2 out of 6 subjects 
receiving GS-9620 experience one or more DLTs considered 
related to study drug.
Statistical Methods:
Safety:
To evaluate overall safety, the incidences of treatment-emergent 
AEs and treatment-emergent laboratory abnormalities will be 
summarized by treatment group.
The proportion of subjects in each treatment group with an AE 
leading to premature discontinuation of study drug and proportion 
of subjects with serious adverse events (SAEs) will be 
summarized by treatment group.
Virology:
The change in plasma HIV-1 RNA and the incidence of 
detectable plasma HIV-1 RNA at each visit will be summarized 
by treatment group.
The change in plasma HIV-1 RNA SCA from pre-dose to 2 days 
post-dose may be explored.
The change in cell (PBMC) associated HIV-1 RNA from 
pre-dose to 2 days post-dose may be explored.
The change in HIV-1 reservoir measured by cell (PBMC)
associated HIV-1 DNA from pre-dose to 2 days post-dose, and in 
Cohorts 4 to 9 by use of secondary assays using stored PBMC 
samples may be explored


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PK:
Exposure parameters of GS-9620 will be summarized using 
descriptive statistics by active treatment. 
PD:
The change from baseline in the levels of serum cytokines will be 
summarized using descriptive statistics by treatment group. The 
post-baseline change and fold induction in mRNA for ISGs will 
be summarized using descriptive statistics by treatment group.
Immunology:
The post-baseline change in peripheral blood immune cell 
numbers for T/B/NK/pDC/mDC including: CD4 and CD8 
populations , CD4/CD8 ratio, CD4 % and lymphocyte activation 
(T, B and NK cells) will be summarized using descriptive 
statistics by treatment group.
The post-baseline change in magnitude and poly-functionality
(Cohorts 4 to 9) of the HIV-1-specific T cell immune response 
may be explored.
TLR7 genotype may be reported and its association with key 
pharmacodynamic and virologic parameters may be explored.
Sample Size:
This is an exploratory study to characterize the safety and efficacy 
of GS-9620; therefore, no power calculation was performed. 
Sample size is determined based on empirical considerations. A 
total of up to 54 subjects (6 per cohort) receiving GS-9620 will 
provide a reasonable preliminary assessment of safety.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C
degree(s) Celsius
F
degree(s) Fahrenheit
ACTG
AIDS Clinical Trials Group
AE
adverse event
AIDS
Acquired Immune Deficiency Syndrome
ALT
alanine aminotransferase (SGPT)
ANOVA
analysis of variance
ART
antiretroviral therapy
AST
aspartate aminotransferase (SGOT)
ATI
analytical treatment interruption
AUC0-t
area under the plasma concentration-time curve from zero
AUC24h
area under the plasma concentration-time curve in 24 hours
AUCtau
area under the plasma concentration versus time curve over the dosing 
interval (tau)
BID
bis in die (two-or twice-a-day)
BLQ
below the limit of quantitation
BUN
blood urea nitrogen
CAVR/CAVD
Cell-associated HIV-1 RNA/DNA
CBC
complete blood count
CDC
Center for Disease Control and Prevention
CFR
Code of Federal Regulations (United States)
Clast
last observed quantifiable concentration of the drug
CLcr
creatinine clearance
Cmax
maximum observed concentration of drug
CNS
central nervous system
CPK
creatine phosphokinase (= creatine kinase, CK)
CSR
clinical study report
Ctau
observed drug concentration at the end of the dosing interval (tau)
CYP3A
cytochrome P450
dL
deciliter(s)
DLT
dose-limiting toxicities
DNA
deoxyribonucleic acid
DTG
dolutegravir
EC
ethics committee
EC50
50% effective inhibitory concentration
ECG
Electrocardiogram
EDC
Electronic data capture
eCRF
electronic case report form(s)


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eGFR
estimated glomerular filtration rate
ESDD
Early Study Drug Discontinuation
EudraCT
European Union Drug Regulating Authorities Clinical Trials
FDA
Food and Drug Administration (United States)
FSH
Follicle stimulating hormone
FTC
emtricitabine
ET
early termination
G
Gram
GCP
Good Clinical Practice (Guidelines)
GGT
gamma-glutamyl transferase (= gamma-glutamyl transpeptidase, GGTP)
GSI
Gilead Sciences, Inc.
HBV
hepatitis B virus
HCV
hepatitis C virus
HBsAg
hepatitis B virus surface antigen
HLT
high level term
HLGT
high level group term
HPF
high-power field
HIV
human immunodeficiency virus
hr
Hour
ICH
International Conference on Harmonization
ICS
intracellular cytokine staining
IC50
50% inhibitory concentration
IEC
Institutional Ethics Committee
IFN
Interferon
IFN-
interferon-alpha
IND
Investigational New Drug (Application)
IP-10
interferon γ–inducible protein-10
IRB
Institutional Review Board
ISGs
interferon-inducible genes
IUD
intrauterine device
IU
international unit
kg
Kilogram
LLN
lower limit of the normal range
LLOD
lower limit of detection
LLT
lower level term
LRA
latency reversal agents
MAD
multiple ascending dose
MedDRA
Medical Dictionary for Regulatory Activities; MedDRA®
mg
Milligram
g
Microgram


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min
Minute
mDC
conventional (myeloid) dendritic cell
mL
Milliliter
mRNA
messenger ribonucleic acid
NK
natural killer (cell)
NDA
New Drug Application
NOAEL
no observed adverse effect level
NRTI
Nucleoside Reverse‑Transcriptase Inhibitors
PEG
pegylated interferon
PBMC
peripheral blood mononucleated cell
PCR
polymerase chain reaction
PD
pharmacodynamics(s)
pDC
plasmacytoid dendritic cell
PK
pharmacokinetic(s)
POC
Proof of concept
PT
prothrombin time
PT
preferred term
PVE
Pharmacovigilance and Epidemiology, Gilead Sciences
PXR
pregnane X receptor
QD
quaque die (one- or once-a-day)
QOD
every other day (dosing)
qPCR
quantitative PCR
RBC
red blood cell (count)
RNA
ribonucleic acid
SAD
single ascending dose
SADR
serious adverse drug reaction
SAE
serious adverse event
SCA
single copy assay
SD
standard deviation
SEC
Safety Evaluation Committee
SIV
Simian immunodeficiency virus
SOC
System Organ Class
SUSAR
Suspected Unexpected Serious Adverse Reaction
T1/2
estimate of the terminal elimination half-life of the drug, calculated by 
dividing the natural log of 2 by the terminal elimination rate constant (z)
Th1/Th2/Th17
T helper cells (1, 2, 17)
Tr1
Type 1 T regulatory cells
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
Treg
T regulatory (cells)


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TBD
to be determined
TFV
tenofovir
TLR
toll-like receptor
ULN
upper limit of the normal range
US
United States
USA
United States of America
vs
versus
WHO
World Health Organization
wt
weight
z
terminal elimination rate constant, estimated by linear regression of the 
terminal elimination phase of the concentration of drug versus time curve


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus type-1 (HIV-1) infection is a life-threatening and serious 
disease that is of major public health interest around the world. There are approximately 
2.4 million people in North America and Western and Central Europe living with HIV-1 and 
36 million people worldwide {Joint United Nations Programme on HIV/AIDS (UNAIDS) 
2016}. Untreated infection leads to deterioration in immune function and death. The availability 
of antiretroviral therapy (ART) has been associated with a dramatic decrease in acquired immune 
deficiency syndrome (AIDS)-related morbidity and mortality {Mocroft 1998, Palella 1998, 
Sterne 2005}.
While ART effectively suppresses HIV replication, HIV infection remains incurable. 
Persistent viral reservoirs fuel rebound viremia when treatment ceases. Despite the availability of 
chronic treatment, morbidity and mortality due to HIV infection remain high due to the latent 
HIV reservoir, which may contribute to ongoing inflammation-driven disease. Current therapy is 
associated with challenges with tolerability, long-term adherence and safety, drug-drug 
interactions, and expense. Persistent HIV infection may also be associated with psychosocial 
stigma. Thus, the discovery and development of therapeutic interventions that can eradicate or 
control HIV reservoirs, leading to long-term ART-free remission or HIV cure, is a major
priority.
Following entry into a target cell, HIV-1 stably integrates into the host genome, thus establishing 
the basis for latent infection and the main barrier to HIV cure. Neither the host immune system 
nor ART can eliminate transcriptionally inactive virus. Therefore, adjunctive therapies that 
efficiently reactivate (“kick”) virus out of this latent reservoir to enable its destruction (“kill”) 
may be required for viral eradication. This “kick and kill” strategy to cure or induce long-term 
HIV remission has been tested in clinical trials of latency reversal agents (LRA) such as histone 
deacetylase inhibitors (HDACi). While short-term treatment with HDACi such as romidepsin 
appears to be safe and may activate viral transcription in individuals virologically suppressed on 
ART, the size of the latent viral reservoir as measured by total peripheral blood mononuclear cell 
(PBMC)-associated HIV-1 DNA or quantitative viral outgrowth assay (QVOA) appears to be 
unchanged {Sogaard 2015}. However, a TLR9 agonist has been dosed in HIV-1 positive 
participants on ART in a single-arm open-label study demonstrating increases in plasma IFN-α 
levels, transcriptional (messenger ribonucleic acid [mRNA] induction of interferon stimulated 
genes (ISGs), activation of pDCs, activation of cytotoxic natural killer (NK) and CD8+ T cells 
with transient increases in plasma HIV-1 RNA in a subset of individuals {Vibholm 2017}. It is 
postulated that a combination of therapies exerting viral latency reversing activity and 
engagement of the host immune system will be necessary to have a demonstrable effect on 
reducing the HIV-1 reservoir. To date there is no fully validated biomarker for the latent HIV-1
reservoir. Therefore, measurement of the time to viral rebound and/or new viral load set-points
following analytical treatment interruption (ATI) is the most accurate endpoint to evaluate the 
efficacy of “kick and kill” interventions. The AIDS Clinical Trials Group (ACTG) has reported 
that ATI can be conducted safely in patients {Bar 2016, Li 2016} and that certain measures of 
the HIV reservoir may be correlated with time to viral rebound {Li 2016}.


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GS-9620 is an orally-administered toll-like receptor (TLR) 7 agonist currently in clinical 
development for the treatment of HIV. In vitro, GS-9620 appears to mediate both HIV-1 “kick” 
and “kill” activity. In a rhesus macaque model of chronic SIV infection, treatment with GS-9620 
or its close analog GS-436986 has also demonstrated the ability to both “kick” and “kill”: 
treatment resulted in transient detection of plasma viremia within 24-72 hours of dosing, 
decreases in ex vivo SIV production from T-cell receptor stimulated PBMC cultures or immune 
cell isolates of peripheral lymph nodes comparing pre-treatment to post-dosing samples and 
a ~0.5 log10 lower viral load set-point after discontinuation of ART {Lim 2018}. Most 
importantly, in a subset of animals, there was a lack of detectable plasma virus (< 50 SIV 
RNA copies/mL) for > 2 years after discontinuation of ART. During the off ART phase,
two animals from one of the studies had no viral rebound after administration of antibodies 
depleting NK and CD8+ lymphocytes or transfer of viral infection after infusion of mononuclear 
immune cells from lymph node and peripheral blood into naïve animals; implying a substantial 
reduction in viral reservoir. The administration of multiple doses of GS-9620 has been shown to 
be safe in clinical studies of healthy subjects (single doses up to 12 mg), and hepatitis B virus 
(HBV)-infected subjects (multiple doses up to 4 mg). This study will therefore investigate the 
safety and efficacy of GS-9620 in HIV-infected individuals who are virologically suppressed on 
ART.
1.2.
GS-9620
1.2.1.
General Information
GS-9620 is an orally-administered TLR7 agonist in development for the treatment of HIV 
infection.
Data in-vitro have shown that GS-9620 is a potent and selective TLR7 receptor agonist with a 
> 30-fold selectivity for TLR7 (32-fold based on EC50 and 81-fold based on minimum 
effective concentration) over toll-like receptor 8 (TLR8), with no detectable stimulation of other 
human TLRs at concentrations up to 100 μM (PC-243-2031).
Nonclinical data in mice and in chimpanzees chronically infected with HBV demonstrated that 
oral administration of GS-9620 induce a type I IFN dependent innate response in the liver, as 
measured by induction of interferon-stimulated genes (ISGs), in the absence of concomitant 
serum detectable levels of IFN-α (i.e. a pre-systemic response) {Fosdick 2013, Lanford 2013}. 
The induction of type I IFN-dependent innate immune responses without the induction of 
detectable systemic IFN-α has been confirmed in healthy human subjects (GS-US-320-0101) and 
patients affected by chronic hepatitis C (GS-US-243-0102) or by chronic hepatitis B 
(GS-US-283-0102, GS-US-283-0106, GS-US-283-1059, and GS-US-283-1062).
For further information on GS-9620, refer to the investigator’s brochure for GS-9620.


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1.2.2.
Preclinical Pharmacology and Toxicology
Preclinical in vivo pharmacology studies in different non-human primate species have 
consistently demonstrated that GS-9620 induces IFN-α, multiple cytokines, chemokines, 
peripheral blood mononuclear cell (PBMC) derived ISG mRNAs and peripheral immune cell 
activation in a dose-dependent manner. Of note, with escalating doses of GS-9620 cynomolgus 
monkeys were shown to have an exaggerated IFN-α response both in vitro and in vivo compared 
to other species (mice, chimpanzees, and humans).
In in vitro PBMC cultures, GS-9620 stimulated markedly higher maximal levels of secreted 
IFN-α in cynomolgus monkey PBMC compared to human PBMC cultures; the in vitro mean 
peak IFN-α was 9105 pg/mL and 1552 pg/mL in cynomolgus monkey and human PBMCs, 
respectively.
Similarly, the mean peak IFN-α concentration in serum following a single oral dose in vivo was 
notably higher in cynomolgus monkeys than healthy human volunteers at an equivalent dose; at 
0.5 mg/kg (human equivalent dose 9.6 mg) the mean peak of serum IFN-α was 4859 pg/mL in 
cynomolgus monkey versus 93.7 pg/mL in human healthy volunteers receiving 12 mg dose 
[study GS-US-243-0101] (human equivalent dose was calculated using a conversion factor 
of 0.32 for cynomolgus monkey and assuming a human body weight of 60 kg {U. S. Department 
of Health and Human Services (DHHS) 2005}).
Single oral doses of GS-9620 given in preclinical studies in cynomolgus monkeys 
(0.05 to 0.5 mg/kg, human equivalent dose 1 – 9.6 mg) and mice (0.3 mg/kg, 
human equivalent dose 1.4 mg) human equivalent dose was calculated using a conversion factor 
of 0.08 for mice and assuming a human body weight of 60 kg {U. S. Department of Health and 
Human Services (DHHS) 2005}) have shown that GS-9620 can induce an innate immunity gene
expression signature, e.g. up-regulation of interferon-stimulated genes (ISG) in the absence of 
detectable serum IFN-α concentrations. These observations are consistent with the concept of a 
pre-systemic response elicited by oral GS-9620.
Body temperature increases were noted in the cardiovascular/respiratory safety pharmacology 
study in cynomolgus monkeys (≥ 0.5 mg/kg) at Cmax exposures that were approximately 
equivalent to the Cmax at the highest dose tested in HBV infected patients 
(4 mg; study GS-US-283-0102). Increases in heart rate were observed concurrently with the 
increases in body temperature and with the peak of IFN-α levels. Of note, body temperature and 
heart rate increase were not seen at the 4-mg dose in the human clinical studies. Increases in 
body temperature and heart rate are well-described side effects of exogenous IFN-α
administration in humans {Vial 1994} and in nonhuman primates {Kubicek 1958, Vial 1994}
and may reflect the sequelae of elevated IFN-α in the cynomolgus monkeys.
In an in vitro electrophysiology assay GS-9620 inhibited the human ether-à-go-go-related gene 
(hERG)-mediated current at an IC50 (50% inhibitory concentration) value that was 
150-fold higher than the Cmax at the highest dose used in HBV infected patients
(4 mg; study GS-US-283-0102). These margins are likely even higher once adjusted for protein 
binding.


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No adverse cardiovascular effects were noted in cynomolgus monkeys at Cmax exposures up to 
1.7-fold higher than projected Cmax (11.97 ng/mL) for a 12 mg dose of GS-9620, the highest dose 
planned to be used in this clinical study. No notable effects on the central nervous or respiratory 
systems were seen in the safety pharmacology studies. Safety pharmacology studies did not 
identify any major effects that would impede the use of GS-9620 in human subjects.
Preclinical toxicology studies were conducted in single dose and multiple dose settings in 
different animal species.
Single Dose Toxicology Studies
Single oral doses of GS-9620 were well tolerated at up to 30 mg/kg and up to 2 mg/kg in mice 
and cynomolgus monkeys, respectively. At higher doses, mortality was noted in single dose oral 
studies in mice at 100 mg/kg (TX-243-2008) or greater (AD-243-2017) and in a single 
woodchuck administered 10 mg/kg orally (AD-243-2014). Additionally, mortality was observed 
following intravenous administration of 3 mg/kg to rhesus monkeys (AD-243-2034). These 
deaths were attributed to high systemic exposure to GS-9620 (≥21-fold higher than the 
AUC0-24 in HBV infected patients [study GS-US-283-0102]; 44.3 pg•h/mL at 4 mg).
Multiple Dose Toxicology Studies
Oral administration of GS-9620 every-other-day (QOD) was well tolerated in the 
4-week and 6-week studies in mice, with the highest doses of 5 and 3 mg/kg QOD, respectively, 
being the no observed adverse effect levels (NOAELs) (Table 1-1).
In cynomolgus monkeys, GS-9620 was well tolerated in the 4-week study with the highest dose 
of 1.5 mg/kg QOD being the NOAEL (Table 1-1).
In the 26-week cynomolgus monkey toxicity study, GS-9620 administration at 
≤0.15 mg/kg/dose was well tolerated. Administration of 0.50 mg/kg every other day 
(reduced to 0.3 mg/kg every other day at Week 11) resulted in morbidity/mortality of 3 animals 
beyond 8 weeks of QOD dosing. In this study the pharmacodynamic effects appeared to increase 
over time and were associated with high levels of circulating IFN-α. Cynomolgus monkeys were 
the most sensitive toxicology species and have an apparent exaggerated IFN-α response to 
GS-9620 (Table 1-1). The observed mortalities in cynomolgus monkeys are consistent with data 
obtained from the New Drug Application (NDA) approvals of peginterferon alpha 2a (Pegasys®) 
and peginterferon alpha 2b (Peg-Intron®) showing that repeated high doses of IFN-α or PEG 
cause a similar spectrum of effects in cynomolgus monkeys as those observed in the 26-week 
toxicology study with GS-9620 {European Medicines Agency (EMA) 2006, Pilaro 2000}. The 
margins of exposure in the preclinical species, based on IFN-α stimulation, range from 0.33 to 
122-fold depending on the duration of exposure due to GS-9620 dosing every other day. Less 
frequent administration, once every other week, in the clinical setting would be expected to 
minimize chronic IFN-α exposure side-effects.


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Table 1-1.
Estimated Margins of GS-9620 Following Oral Administration at the 
Highest Anticipated Human Dose
Species
Duration
Dose
(mg/kg/dose)
AUC0-taua
ng•h/mL
Cmaxa
ng/mL
Mean 
Peak 
IFN-α 
pg/mL
Margin of Exposure
AUCinfb
Cmaxb
IFN-αc
Mouse
QOD x 4 weeks
5
(NOAEL)
43.5
13.4
237
0.3x
1.1x
2.4x
QOD x 26 weeks
3
(NOAEL)
15.8
6.64
60.7
0.1x
0.6x
0.6x
Cynomolgus 
Monkey
QOD x 4 weeks
1.5
(NOAEL)
73.8
86.7
11900
0.5x
7.2x
122x
QOD x 26 weeks
0.15
(NOAEL)
0.171
0.077
32
0.001x
0.006x
0.33
0.5/0.3
1.82d
0.504d
2085d
0.013x
0.04x
21x
a
Males and females combined, Week 4 or Week 26 as applicable
b
Margins of exposure were calculated using clinical GS-9620 Cmax and AUCinf at 12 mg of 12.0 ng/mL and 140 ng•h/mL, 
respectively (GS-US-243-0101)
c
Margins of exposure were calculated using the mean peak for IFN-α (97.3 pg/mL) from healthy subjects dosed with 12 mg 
GS-9620 (GS-US-243-0101)
d
Week 17 at 0.3 mg/kg
Source: Studies TX-243-2005, TX-243-2011, TX-243-2004, TX-243-2012
Monotherapy Proof-of-Concept Studies in Monkeys
In a rhesus macaque model of chronic SIV infection, treatment with GS-9620 or its close analog 
GS-436986 has also demonstrated the ability to both “kick” and “kill”. Treatment resulted in 
transient detection of plasma viremia within 24-72 hours of dosing, decreases in ex vivo SIV 
production from T-cell receptor stimulated PBMC cultures or immune cell isolates of peripheral 
lymph nodes comparing pre-treatment to post-dosing samples and a ~0.5 log10 lower viral load 
set-point after discontinuation of ART {Lim 2018}. Most importantly, in a subset of animals, 
there was a lack of detectable plasma virus (< 50 SIV RNA copies/mL) for > 2 years after 
discontinuation of ART. During the off ART phase two animals from one of the studies had no 
viral rebound after administration of antibodies depleting NK and CD8+ lymphocytes or transfer 
of viral infection after infusion of mononuclear immune cells from lymph node and peripheral 
blood into naïve animals; implying a substantial reduction in viral reservoir.
1.2.3.
Clinical Trials of GS-9620
As of 27 March 2018, 4 Phase 1 clinical studies, 1 Phase 2 clinical study, and 1 registry study 
have been completed in which 55 healthy subjects, 42 HCV infected subjects, and 230 subjects 
with chronic hepatitis B (CHB) (189 virologically suppressed and 41 treatment naive subjects) 
were dosed with GS-9620. In addition, a Phase 2 clinical trial (GS-US-283-1059) in virologically 
suppressed CHB subjects has completed dosing and a Phase 1 clinical trial (GS-US-382-3961) in 
HIV-1 infected controllers on ART is currently on-going. In these studies, single doses ranged 
from 0.3 mg to 12 mg in healthy volunteers, and from 0.3 mg to 4 mg in HCV- and 
HBV-infected subjects. Multiple doses (two doses one week apart and up to 12 doses one week 
apart) were assessed in HCV-infected and HBV-infected subjects and ranged from 0.3 mg to 
4 mg.


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In HIV-infected subjects, multiple doses of GS-9620 ranging from 1 mg to 6 mg were assessed, 
with the 8 mg dosing cohort currently in progress.
1.2.3.1.
GS-US-243-0101
Study GS-US-243-0101 was a first-in-human, randomized, double-blind, placebo-controlled, 
single ascending dose (SAD) study of GS-9620 in 75 healthy male and female subjects. The 
primary objective of the study was to evaluate the safety and tolerability of GS-9620 and the 
secondary objectives were to characterize the plasma PK/PD profile of GS-9620. Doses used 
were: 0.3, 1, 2, 4, 6, 8, and 12 mg.
The treatment was generally well tolerated. There were no Grade 4 AEs or serious adverse 
events (SAEs) reported, and most AEs were mild. No individual subject discontinued due to AEs 
or laboratory abnormalities. Treatment-emergent Grade 3 AEs included pyrexia in 2 subjects 
who received GS-9620 12 mg. A higher incidence of flu-like symptoms was also reported in 
subjects administered the higher doses (8 and 12 mg). Myalgia and headache were reported by 
subjects in both the 8 and 12 mg cohorts, while pyrexia and chills were only reported by subjects 
in the 12 mg cohort.
Plasma concentrations of GS-9620 peaked between 1.5 and 6 hours after dosing and declined 
gradually over 48 hours. The mean maximum plasma concentration (Cmax) ranged from 
184.2 pg/mL at the 0.3 mg dose to 11.97 ng/mL at the 12 mg dose. Exposures were higher in the 
fasted state than in the fed state. After the 1 mg, 2 mg, and 4 mg doses, GS-9620 was detectable 
at 48 hours after dosing and had a median terminal half-life between 17.16 and 26.96 hours.
Three ISGs were analyzed: ISG15, MX-1 and OAS-1. Significant ISG induction was observed at 
the 2-mg dose and above. ISG15 mRNA expression showed the highest induction compared to 
MX-1 and OAS-1. Serum IFN-α was detected transiently in subjects who received the 
8 or 12 mg doses, and only the 12 mg cohort had a >2-fold mean change in serum IFN-α from 
baseline. A dose-dependent induction was observed for serum IP-10 but not for IFN-α or TNF-α. 
Dose-dependent T cell activation was also observed at the 2 mg dose and above.
In summary, single doses of GS-9620 up to 12 mg were well tolerated, with significant ISG 
induction and T cell activation at doses of 2, 4, and 6 mg in the absence of detectable 
serum IFN-α or systemic AEs.
1.2.3.2.
Other Phase 1 studies
The following studies have also demonstrated good tolerability of GS-9620 (see IB for details):

GS-US-243-0102: A Phase 1b ascending, single and multiple-dose study evaluating the 
safety, PK, PD, and antiviral activity in treatment-naive HCV subjects.

GS-US-283-0102: A Phase 1b ascending, single and multiple-dose study evaluating the 
safety, PK/PD, and antiviral activity in virologically-suppressed HBV subjects.


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
GS-US-283-0106: A Phase 1b ascending, single and multiple-dose study evaluating the
safety, PK/PD, and antiviral activity in treatment-naive HBV subjects.

GS-US-283-0110: An observational registry study of subjects who did not achieve loss of
HBsAg and sustained HBV viral load reduction below the level of quantitation in 
Gilead-Sponsored trials of GS-9620 in subjects with chronic HBV infection.
1.2.3.3.
GS-US-283-1059
GS-US-283-1059 was a Phase 2, randomized, double-blind, placebo-controlled multi-center 
study to evaluate the safety and efficacy of GS-9620 in HBV-infected subjects who are 
virologically suppressed. In this study, approximately 162 subjects received weekly dosing with 
GS-9620 (1, 2 or 4 mg) or placebo for a total of 4 (Cohort A), 8 (Cohort B) or 12 (Cohort C)
weeks. The efficacy of GS-9620 was evaluated by assessing the change from baseline to 
Week 24 in HBsAg levels. Overall, once-weekly dosing of GS-9620 1, 2, or 4 mg for 4, 8, or 
12 weeks was generally well tolerated in virologically-suppressed subjects with CHB on OAV. 
Most subjects had Grade 1 (mild) AEs and, except for the Cohort C 4 mg group in which a 
higher proportion of subjects had Grade 2 (moderate) and 3 (severe) AEs compared with 
Cohorts A and B. No other dose-related or treatment duration-related safety findings were 
observed. No Grade 4 (life threatening) AEs were reported in any of the cohorts. Four subjects 
had SAEs, 3 of these subjects had AEs that led to discontinuation of study drug, and 3 of the 
4 subjects had study drug interrupted due to AEs. No deaths occurred in any study participant.
Two subjects interrupted study treatment after having experienced SAEs due to an overdose 
caused by a dispensing error at the study site. One of these subjects randomized to 2 mg
GS-9620 mistakenly received 10 mg and one subject randomized to 4 mg mistakenly received
20 mg. These 2 subjects experienced transient Grade 3 AEs of flu-like symptoms, , and decline 
in lymphocytes count; the subject who received 10 mg experienced Grade 3 AEs of pyrexia, 
chills and hot flush, all SAEs that were assessed as related to study drug by the investigator. The 
subject who received 20 mg experienced SAEs of Grade 3 AE of tremor and Grade 2 
hypotension requiring hospitalization. This subject also experienced additional Grade 2 AEs of 
abdominal pain, diarrhea, and vomiting, and an increase in ALT value. For both subjects, each of 
the AEs resolved within24 hours after overdose. A meeting of the Data Monitoring Committee
reviewed these events and determined them to be due to the overdose of GS-9620 with expected
effects of interferon-alpha induction and cytokine release and allowed for the study to proceed as
planned. The other two subjects with SAEs were in Cohort C (cataract, which was reported in 
one subject with a medical history of cataract, and cholecystitis, which was reported in the other 
subject). The subject who experienced cholecystitis also withdrew from study drug and the 
study.
Most AEs reported were Grade 1 or Grade 2 in severity. No Grade 4 (life threatening) AEs 
occurred in any of the cohorts. For Cohort A, 1 subject in each group had Grade 3 AEs. None of 
the Grade 3 AEs led to withdrawal from study drug and none occurred in more than 1 subject. 
All of the Grade 3 AEs resolved. Excluding the 2 overdosed subjects discussed above, 2 subjects 
(placebo and GS-9620 1 mg) experienced transient Grade 3 AE of anxiety and diarrhea, 
respectively, during the treatment period with GS-9620/placebo; both AEs resolved within 


GS-9620
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Final
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Amendment 7
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24 hours. For Cohort B, no subjects had Grade 3 AEs. For Cohort C, 6 subjects had Grade 3 
AEs: 2 subjects in the GS-9620 1 mg group, 1 subject in the GS-9620 2 mg group, 2 subjects in 
the GS-9620 4 mg group, and 1 subject in the placebo group. Two subjects, both in the GS-9620 
4 mg group, with Grade 3 AEs (cholecystitis [discussed above] and panic attack) withdrew from 
the study and study drug.
Overall, patients from both the GS-9620-treated and placebo groups experienced a similar 
number of treatment emergent AEs (TEAEs) (68% study drug vs. 70% placebo). Upon 
assessment of relation to study drug, 37% of patients treated with GS-9620 reported at least one 
AE compared to 50% of placebo patients, all of which were mild to moderate in severity. No 
dose-dependency for AEs was observed across cohorts. The most commonly reported related 
AEs (for ≥2 or more patients) in Cohort A were fatigue (4 of 16 [25.0%] subjects) and diarrhea, 
headache, oropharyngeal pain, pruritus, and pyrexia (each of which occurred in 2 of 16 patients 
[12.5%]) (1-mg group); headache (4 of 15 [26.7%] subjects), fatigue (3 of 15 [20.0%] patients) 
and chills (2 of 15 [13.3%] patients) (2-mg group); and fatigue and pyrexia (each in 3 of 16 
[18.8%] patients) and headache (2 of 16 [12.5%] patients) (4-mg group). In Cohort B, headache 
(6 of 18 [33.3%] patients), nausea (3 of 18 [16.7%] patients) and acne, dizziness, fatigue, 
insomnia, and oropharyngeal pain (each in 2 of 18 [11.1%] patients) (1-mg group); headache and 
dizziness (each in 2 of 17 [11.8%] patients) (2-mg group); and headache (4 of 17 
[23.5%] patients) and fatigue, influenza-like illness, and rhinorrhea (each in 2 of 17 [11.8%] 
patients) (4-mg group) were most common. In Cohort C, headache, fatigue, influenza-like illness 
(each in 4 of 16 [25.0%] patients) and asthenia, pyrexia and somnolence (each in 2 of 16 [12.5%] 
patients) (1-mg group); abdominal pain upper and headache (each in 3 of 17 [17.6%] patients) 
and fatigue (2 of 17 [11.8%] patients) (2-mg group); and asthenia (5 of 14 [35.7%] patients), 
headache, influenza-like illness, and pyrexia (each in 3 of 14 [21.4%] patients) and myalgia (2 of 
14 [14.3%] patients) (4-mg group). Headache was the most commonly reported placebo group 
AE (40-50% of patients).
Among the patients dosed with GS-9620, treatment-emergent graded ALT elevations were seen 
in 5 subjects (4 subjects with Grade 1 and one subject with Grade 2). All grade 1 elevations were 
transient (1 placebo, 1 GS-9620 2 mg, and 2 GS-9620 4 mg) and the grade 2 elevation occurred 
22 days after the last dose of GS-9620 4 mg and reduced to grade 1 elevation 3 days later.
Please refer to the current GS-9620 Investigator’s Brochure for the treatment of chronic hepatitis 
B virus infection for additional information regarding the above studies.
1.2.3.4.
GS-US-283-1062
This Phase 2, randomized, double-blind, placebo-controlled study is being conducted to evaluate 
the safety and efficacy of administering either 1 mg, 2 mg or 4 mg of GS-9620 orally once a 
week (every 7 days) for 12 doses (Weeks 0-11) in adult subjects with CHB who were not 
currently on treatment for CHB. 192 subjects were randomized in a 1:2:2:2 ratio to 1 of the 
4 treatment arms (placebo, GS-9620 1 mg, 2 mg, or 4 mg) for weekly dosing for a total of 
12 doses and stratified by HBeAg status (positive versus negative) and ALT (> versus 
≤19 IU/mL for female; > versus ≤ 30 IU/mL for male). All subjects were also treated with TDF 
300 mg oral daily for 48 weeks.


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Amendment 7
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Preliminary interim safety results from Week 48 show that overall, once-weekly dosing of 
GS-9620 1, 2, or 4 mg was generally well tolerated. 65% of subjects overall had at least 1 AE 
during the study and most of the reported AEs were Grade 1 (mild) or 2 (moderate) in severity. 
Overall, the majority of subjects had Grade 1 (mild) or moderate (Grade 2) AEs. Six subjects 
experienced Grade 3 (severe) AEs. No Grade 4 (life threatening) AEs were reported in any of the 
treatment groups. 
Four subjects had treatment-emergent SAEs: an SAE of laceration (deep laceration on the right 
foot) on Day 133 which resolved on Day 252, an SAE of asthma (worsening of asthma) on 
Day 257 which resolved on Day 288, an SAE of breast cancer on Day 422 continuing at the time 
of the interim data cut, and an SAE of abdominal pain (exacerbation of chronic generalized 
abdominal pain) on Day 71 which resolved on Day 85. All SAEs were considered by the 
investigator to be unrelated to study drugs or to study procedures. No action was taken with 
study drugs, with the exception of TDF dose interruption for the abdominal pain case and dose 
withdrawn for the breast cancer case. No deaths occurred.
Six subjects overall (3.1%) discontinued study drug due to an AE, all of which were considered 
related to study drugs by the investigator.
Across the treatment groups, most laboratory abnormalities were Grade 1 or 2 in severity. 
Five subjects had ALT ≥10x ULN and thirty had ALT between 3x ULN and < 10x ULN and 
> 2x nadir.
1.2.3.5.
GS-US-382-3961
This ongoing Phase 1b, randomized, double-blind, placebo-controlled study is being conducted
to evaluate the safety and efficacy of GS-9620 in antiretroviral treated HIV-1 infected 
controllers. The study is conducted in two periods. In Period 1, up to 30 subjects will be 
randomized 2:1 to receive GS-9620 or placebo-to-match. All subjects will receive up to 10 doses 
of their assigned study treatment administered orally every 14 days. Subjects will continue to 
take their prescribed ART during Period 1. In Period 2, all subjects will discontinue ART and be 
monitored for rebound in HIV-1 plasma viremia. Enrollment is ongoing and several subjects 
have completed dosing (4-6 mg) and are undergoing ART interruption (Period 2).
1.3.
Rationale for This Study
Despite the extensive advances made in the treatment of chronic HIV-1 infection, eradication of 
the latent HIV-1 reservoir is still needed to achieve a cure that abrogates the requirement for 
lifelong ART. To this end, “kick and kill” strategies to reactivate and target latent virus have 
been tested in a number of clinical trials, but none have resulted in lasting virologic remission. 
GS-9620 is a promising candidate for this approach given the demonstration of both SIV 
reactivation (as measured by transient plasma viremia in the presence of ART), decrease in SIV 
reservoir (as measured by proviral DNA in PBMCs, lymph node and colon), and ~0.5 log 
reduction in SIV set point relative to pre-ART plasma viral load set point following ART 
interruption in studies of SIV-infected rhesus macaques treated with GS-436986, a close analog 
of GS-9620. In a second study in SIV-infected rhesus on ART the TLR7 agonists GS-9620 or 
GS-436986 administered for 10 or 19 doses produced transient plasma viremia within 


GS-9620
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Amendment 7
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24-72 hours after dosing. Sampling PBMCs and immune cell isolates from lymph node biopsies 
prior to TLR7 agonist administration and after completing all doses demonstrated a decrease in 
the amount of SIV production following T-cell receptor stimulation. Interestingly, two of these 
animals, one from the GS-9620 dosing group and one from the GS-436986 dosing group had no 
detectable ex vivo SIV production from both PBMCs and isolated immune cells from lymph 
node biopsies. Most importantly, after ART discontinuation these same two animals had no 
detectable plasma virus (< 50 SIV RNA copies/mL) rebound which has been sustained for at 
least twenty four months. These results suggest the possible use of TLR7 agonists in 
combination with ART toward reduction of HIV reservoirs and ultimately finite therapies for 
HIV-1 infection. In addition, GS-9620 appears to be safe in healthy and HBV-infected subjects.
1.4.
Rationale for Dose Selection/Dosing Interval
In 50 HCV and in 100 HBV patients, doses of up to 4 mg of GS-9620 were evaluated, either as a 
single dose or two doses one week apart. Safety data from these studies demonstrated that 
GS-9620 is well-tolerated with no evidence of dose dependent adverse events or laboratory 
abnormalities that are consistent with systemic immune activation such as flu-like symptoms, 
hematologic reductions or increases in liver enzymes including transaminases. In the majority of 
patients there was no detectable IFN-α in serum, consistent with the mechanism of action of 
pre-systemic innate immune system activation in the GALT and/or in the liver. Evidence of 
biological activity was observed in a dose dependent manner in these studies, with maximal 
induction of ISG15 occurring within 48 hours and return to baseline levels of expression within 
168 hours (7 days). In addition, the safety of a weekly dosing interval was supported by the 
observed elimination half-life (median range 8 to 25 hours for 1, 2, or 4 mg doses in HBV- or 
HCV-infected subjects) and that no accumulation of GS-9620 occurred following once-weekly 
dosing.
A dosing schedule of once every 2 weeks is planned for this protocol in order to verify the 
resolution of GS-9620-induced HIV-1 viremia prior to additional dosing. This schedule is more 
conservative than the weekly administrations used in the Phase 1 evaluations across the 
above-referenced studies in chronic hepatitis B and C patients.
In the current study GS-US-382-1450, approximately 32 HIV-1-infected subjects have received 
biweekly dosing with GS-9620 (1, 2 and 4 mg) or placebo for a total of 6 doses, and GS-9620 
6 mg or placebo for a total of 10 doses. No safety issues including dose-limiting toxicities were 
identified; however, pharmacodynamic and virologic effects were limited. The protocol-defined 
safety evaluation committee (SEC) recommended proceeding with enrollment of the 6 mg cohort 
on February 7, 2017. In the 6 mg dose cohort (Cohort 4) of this study, 6 subjects experienced 
treatment-emergent AEs. Three of these subjects had AEs which were considered to be related to 
study drug by the investigator: one subject had decreased concentration, vivid dreams, sweats, 
and fatigue; another subject had headache and increased peripheral neuropathy; the third subject 
had fatigue, myalgia, and nasal congestion. All of these AEs were grade 1 or 2 and all resolved 
during the dosing period. There have been no grade 3 or 4 AEs, AEs leading to study drug 
discontinuation, SAEs or deaths. The protocol-defined SEC reviewed blinded safety data from 
the 6 mg cohort on 25 September 2017 and recommended proceeding with the addition of the 
8 mg cohort (Cohort 5). In the 8 mg dose cohort (Cohort 5) of this study, a total of 8 subjects 


GS-9620
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Amendment 7
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have been enrolled and are currently being dosed with study drug. At the time of the interim 
safety data cut (30 April 2018), all subjects had completed 5 out of 10 doses, and 3 subjects had 
completed 6 doses. There have been no grade 3 or 4 AEs, AEs leading to study drug 
discontinuation, SAEs or deaths. Three subjects have had mild AEs considered related to study 
drug by the investigator. These AEs include chills and malaise in one subject, pyrexia and 
myalgia in another subject, and headache in the last subject. All resolved within one day and 
have not recurred after Dose 3, thus far. If the SEC recommends proceeding with the 10 mg dose
escalation of GS-9620, Cohort 6 will be opened for enrollment with the potential to escalate to 
the 12 mg dose of GS-9620, starting with dose 4 (out of 10 total doses of GS-9620). In Cohort 6, 
the SEC will review blinded safety data after all subjects have completed three doses of 10 mg of 
GS-9620 or placebo. Dose escalation to 12 mg of GS-9620 within Cohort 6 will only be initiated 
if SEC approval is obtained.
The highest GS-9620 dose planned to be assessed in this clinical study may be up to 12 mg. 
Dose selection has been based on the results from the study in healthy volunteers 
(GS-US-243-0101) that showed dose-dependent ISG mRNA induction from 0.3 mg up to 12 mg
in the absence of dose-dependent induction in serum IFN-α. As described above, dose escalation 
to Cohort 6 (GS-9620 10 mg) for the proposed study is also based on interim safety data from the
ongoing 8 mg cohort (Cohort 5) as described above.
 
 
With regard to the proposed adaptive cohorts, food affects absorption of GS-9620 and 
administration of GS-9620 4 hours post-ingestion of a high fat meal in Study GS-US-243-0101 
resulted in approximately 30% reduction of systemic exposures of GS-9620, minimal effect on 
PD biomarkers and improved tolerability. Dosing GS-9620 with an acidic solution may improve 
the solubility and absorption of the compound. 
 
 
 
 
1.5.
Rationale for Biomarker Testing
It is hypothesized that the mechanism of action of GS-9620 is partly due to the initial activation 
of the innate immune system via TLR7 positive pDCs, promoting activation and maturation of 
pDCs and the release of antiviral cytokines and chemokines including IFN-α. The matured pDCs 
present HIV antigens to HIV-specific CD4 and CD8 T cells, thereby enhancing the HIV-specific 
adaptive response (cytotoxic CD8 T cells). These multifaceted effector mechanisms 
(cytotoxic CD8 T cells, NK cells, and antiviral cytokines) together strengthen the lymphocyte 
anti-HIV immune response and may lead to lowering the viral set point.
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To provide proof of concept on the mechanism of action of GS-9620 in HIV-1 infected patients, 
several exploratory immunological biomarkers will be examined and listed below. The testing 
outlined below is based upon the current state of scientific knowledge. It may be modified during 
or after the end of the study to remove tests no longer indicated and/or to add new tests based on 
the growing state of the art knowledge. The following samples and biomarkers will be examined:

Whole blood samples will be collected for interferon stimulated gene (ISG) mRNA 
measurements 

Whole blood samples will be collected, mononuclear cells isolated, and frequency and 
phenotype (activation, maturation, exhaustion) of lymphocyte populations will be 
enumerated by flow cytometry.

Whole blood samples will be collected, mononuclear cells isolated and the frequency of 
HIV-specific T-cells will be quantitated by ex vivo IFN-γ ELISPOT assay and 
poly-functional ICS.

Levels of cytokines, chemokines, and inflammatory markers will be quantified by 
immunoassays.

Stool samples will be collected in Cohorts 5 to 9 for testing of the fecal microbiome and 
exploratory analysis
1.6.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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Amendment 7
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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the safety and tolerability of GS-9620 at escalating, multiple doses of GS-9620
in HIV-1 infected virologically suppressed adults on ART

To evaluate the virologic effect of GS-9620 as measured by changes in plasma HIV-1 RNA
The secondary objectives of this study are:

To evaluate the plasma pharmacokinetics (PK) of GS-9620

To evaluate the pharmacodynamics (PD) of GS-9620 as measured by changes in 
interferon-stimulated genes (ISGs) and serum cytokines in whole blood compared to placebo

To evaluate effects of GS-9620 on whole blood immune cell activation (T cell, B cell, 
NK cell)
The exploratory objectives of this study are:
 
 
 
 
 
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Amendment 7
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3.
STUDY DESIGN
3.1.
Endpoints
The primary safety endpoint of this study is:

Incidence of treatment-emergent SAEs and all treatment-emergent adverse events
The primary virology endpoint of this study is:

Maximum change from baseline in plasma HIV-1 RNA at any post-dose time point
The secondary endpoints of this study are:

Change from baseline in plasma HIV-1 RNA at post-baseline visits 

Proportion of subjects with plasma HIV-1 RNA > 50 copies/mL at any post-dose timepoint
The exploratory endpoints of this study are:
 
 
 
 
3.2.
Study Design
This protocol describes a randomized, double-blind, multi-cohort dose escalation study that will 
evaluate the safety and efficacy of 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg and 12 mg of GS-9620 
or placebo administered orally every other week for 71 days (for Cohorts 1 to 3), 127 days 
(for Cohorts 4 to 6), 
in HIV-1 infected, ARV-treated,
virologically suppressed adults. For each cohort, subjects will be randomized in a 6:2 ratio to 
receive GS-9620 or placebo. For Cohorts 5, 6
 eight unique subjects per cohort will receive 
GS-9620 or placebo after an overnight fast. 
All subjects will receive a total of 6 doses (for Cohorts 1 to 3), 
10 doses (for Cohorts 4 to 9) of their assigned study treatment administered once every other 
week. For all subjects in Cohort 6, Dose 4 (Day 43) will occur after SEC review has been 
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completed. If dose escalation is approved by the SEC, subjects in Cohort 6 will receive 12 mg of 
GS-9620 or placebo from Doses 4 to 10; if dose escalation is not approved by the SEC, subjects 
will continue receiving 10 mg of GS-9620 or placebo from Doses 4 to 10. 
 
 
Subjects will continue their 
ARV regimen for the entire study duration.
Subjects will return for an end of study visit 30 days after the last dose of study drug is taken.
Enrollment will initially be opened for Cohort 1 only. The SEC will review study progress,
safety and virology data of enrolled subjects. After all subjects in a cohort have received at least 
three doses (Cohorts 1 to 3, and 6) or five doses (Cohorts 4 to 5), the SEC will review safety data 
from that cohort, including adverse events, clinical laboratory results and plasma HIV-1 RNA, 
before approving the next dose escalation. 
 
A 
cohort may be suspended if ≥2 out of 6 subjects receiving GS-9620 experience one or more 
DLTs considered related to study drug. The SEC will consist of members not directly involved 
with the conduct of the study. Please refer to the SEC Charter for additional details.
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GS-9620 
Protocol GS-US-382-1450 
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Gilead Sciences, Inc. 
Amendment 7 
Figure 3-1. 
High-Level Study Schema 
Cohort 1: GS-0020 1mg : placebo (6:2) 
1 
2 
Cohort 2: GS-9620 2mg : placebo (6:2) 
s-
, 
Cohort 3: GS-9620 4mg : placebo (6:2) 
Cohort 5 : GS-8620 3mg : placebo (6:2) 
Dose.: 
1
23.t5 6789
10 
< ,. __ ., Cohort 6: GS-9620 10mg with possible escalation 
to 12mg: placebo (6:2) 
' 
2 
3 i 45G7
8910 
~Jcohort s: GS-9620 12mg : placebo (6:2) I 
Dose-: 
45678910 
Figure 3-2. 
Cohort 6 Visit Schema 
D&y -13 
Ser@'l?nlng 
Druil! 1 
Dose 2 
DosE< 3 
Dose 4-
Dose S 
Dav I 
Day 15 
Day 29 
Day 43 
Day· 57 
12 mgdosin~ 
3.3. 
Study Treatments 
CONFIDENTIAL 
IJ<>,e 6 
Day71 
Notes: 
Dose 7 
Dos.e 8 
Dose 9 
Dose 10 
Dav 85 
Dav 99 
Oe,y 113 
Day 121 
Cohort 6 will con,ist of S ,ubject. (3:l). Preliminary/(iFL) 
safety data of 8 subjects up to Dose 3 Day29 will be 
reviewed by the protoool-defined SEC. Dose escalation 
to 12mg (Dose 4-10) wit hin the cohort will be initiated 
only ofter SEC opprovo l. 
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For each cohort, 8 subjects will be randomized in a 6:2 ratio to receive GS-9620 or placebo. All 
subjects will receive a total of 6 doses (for Cohorts 1 to 3), 10 doses (for Cohorts 4 to 6), 
 
of their assigned study treatment administered once every other 
week. Subjects will continue their existing ARV regimen for the entire study duration.
Cohort 1 (n=8): GS-9620 1 mg (n=6) or placebo-to-match (n=2)
Cohort 2 (n=8): GS-9620 2 mg (n=6) or placebo-to-match (n=2)
Cohort 3 (n=8): GS-9620 4 mg (n=6) or placebo-to-match (n=2)
Cohort 4 (n=8): GS-9620 6 mg (n=6) or placebo-to-match (n=2)
Cohort 5 (n=8): GS-9620 8 mg (n=6) or placebo-to-match (n=2) administered following
overnight fasting 
Cohort 6 (n=8): GS-9620 10 mg with potential to escalate to 12 mg (n=6) or placebo-to-match 
(n=2) administered following overnight fasting
 
 
 
 
3.4.
Duration of Treatment
The treatment duration is 71 days (Cohorts 1 to 3), 127 days (Cohorts 4 to 6), 
 
 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately up to seventy two (72) subjects who meet the inclusion/exclusion criteria will be 
enrolled. Subjects who discontinue study participation before completion of dosing for reasons 
other than study-treatment related adverse events may be replaced.
4.2.
Inclusion Criteria (All Cohorts)
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2) HIV-1 infected males and non-pregnant, non-lactating females ≥ 18 years at 
Pre-Baseline/Day -13
3) On antiretroviral (ARV) regimen for ≥ 12 consecutive months prior to Pre-Baseline/Day -13
a) The following agents are allowed as part of the current ARV regimen: NRTIs, raltegravir, 
dolutegravir, rilpivirine, and maraviroc
b) The following agents are NOT allowed as part of the current ARV regimen: 
HIV protease inhibitors (including low dose ritonavir), cobicistat-containing regimens, 
elvitegravir, efavirenz, etravirine, and nevirapine
c) A change in ARV regimen ≥ 45 days prior to Baseline/Day 1 for reasons other than 
virologic failure (e.g. tolerability, simplification, drug-drug interaction profile) is allowed
4) Plasma HIV-1 RNA levels < 50 copies/mL at screening
5) Documented plasma HIV-1 RNA levels < 50 copies/mL (according to the local assay being 
used) for ≥ 12 months preceding the screening visit (measured at least twice using a licensed 
assay with a lower limit of quantitation of at least 40 copies/mL) 
a) Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or
“blip”) prior to screening are acceptable. (If the lower limit of detection of the local 
HIV-1 RNA assay is < 50 copies/mL, the plasma HIV-1 RNA level cannot exceed 
50 copies/mL on two consecutive HIV-1 RNA tests)
b) If ARV regimen is changed ≥ 45 days prior to Pre-Baseline/Day -13, plasma HIV-1 RNA 
<50 copies/mL at Pre-baseline/Day -13 visit is required.
6) No documented history of resistance to any components of the current ARV regimen


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7) Availability of a fully active alternative ARV regimen, in the opinion of the Investigator, in 
the event of discontinuation of the current ARV regimen with development of resistance
8) Hemoglobin ≥ 11.5 g/dL (males) or ≥ 11 g/dL (females)
9) White blood cell ≥ 4000 cells/L
10) Platelets ≥150,000/mL
11) Absolute Neutrophil Count ≥ 1500 cells/L
12) CD4 count ≥ 400 cells/L
13) Albumin ≥ 3.9 g/dL
14) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2 × upper limit of 
normal (ULN)
15) Estimated GFR ≥ 60 mL/min according to the Cockcroft-Gault formula for creatinine 
clearance {Cockcroft 1976}:
i.
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
ii. Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
16) All subjects must agree to utilize male or female condoms during sexual activity, or practice
sexual abstinence for the duration of the study.
17) Females of childbearing potential must agree to utilize highly effective contraception 
methods (as described in Appendix 5) or be non-heterosexually active or practice sexual 
abstinence from screening through the duration of study treatment and for 36 days following 
the last dose of study drug.
a) Female subjects who utilize hormonal contraceptive as one of their birth control methods 
must have used the same method for at least three months prior to study dosing
b) Female subjects who have stopped menstruating for ≥ 12 months but do not have 
documentation of ovarian hormonal failure must have a serum follicle stimulating 
hormone (FSH) level at screening within the post-menopausal range based on the 
Central Laboratory reference 
18) Male subjects must agree to utilize a highly effective method of contraception during 
heterosexual intercourse (as described in Appendix 5) or be non-heterosexually active, or 
practice sexual abstinence from screening throughout the study period and for 90 days 
following discontinuation of investigational medicinal product


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4.3.
Exclusion Criteria (All Cohorts)
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) A new AIDS-defining condition diagnosed within 90 days prior to screening 
(refer to Appendix 6)
2) Hepatitis B surface antigen (HBsAg) positive
a) Positive anti-HBs antibody and negative HBsAg results are acceptable
3) Hepatitis C antibody (HCVAb) positive
a) Positive anti-HCV antibody and negative HCV PCR results are acceptable
4) Documented history of pre-ART CD4 nadir < 200 cells/L
a) Unknown pre-ART CD4 nadir is acceptable
5) History of autoimmune disease (e.g. lupus erythematosus, rheumatoid arthritis, inflammatory 
bowel disease, sarcoidosis, moderate or severe psoriasis)
6) Acute febrile illness within 35 days prior to Pre-Baseline/Day -13
7) Participation in any other clinical trial (including observational trials) without prior approval 
from the sponsor is prohibited while participating in this trial
8) Current alcohol or substance use judged by the Investigator to potentially interfere with 
subject study compliance
9) History or presence of allergy or intolerance to the study drug or their components
10) Any vaccination or immunomodulatory concomitant medication within 30 days prior to
Pre-Baseline/Day -13. Elective vaccination (e.g. flu shot, hepatitis A or B vaccine) during the
course of the study will require prior approval from Sponsor.
11) Use of any other prohibited concomitant medications as described in Section 5.4 within 
14 days prior to Baseline/Day 1 visit. Refer to the current Prescribing Information for the 
medications that are contraindicated with the current ARV regimen
12) Any other clinical condition 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.


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4.4.
Other Protocol Restrictions
Subjects will be encouraged to avoid strenuous or prolonged exercise, as well as saunas, 
steam baths, and sunbathing or other prolonged UV exposure, (eg in a tanning salon) from the 
screening evaluation until completion of end of study procedures, as these activities are known to 
affect certain clinical laboratory test parameters, (eg CPK) and may provide false indicators of a 
potentially treatment-related toxicity.
Subjects will also be prohibited from blood donation (in excess of that required for clinical care) 
within 30 days prior to Screening and 30 days after end of study.
Smokers and other current tobacco users should keep their tobacco use relatively consistent 
while enrolled in the study. Non-smokers or ex-smokers should not start or resume smoking.
Other restrictions include all illegal or illicit drug use and use of prescription drugs outside the 
care of the prescribing physician.


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding and Treatment Codes
The randomization will be performed via an Interactive Web Response System (IWRS), whereby 
study treatment will be assigned to subjects according to the randomization schedule.
The subject number assignment may be performed up to 3 days prior to the in-clinic
Pre-Baseline/Day -13 visit, provided that all other screening procedures have been completed 
and subject eligibility has been confirmed. Once a subject number has been assigned, it will not 
be reassigned to any other subject.
Eligible subjects (n= 72, 8 per cohort) will be randomized in a 6:2 ratio to receive GS-9620 
1 mg or placebo (Cohort 1), 2 mg or placebo (Cohort 2), 4 mg or placebo (Cohort 3), 6 mg or 
placebo (administered as three 2 mg tablets) (Cohorts 4
 8 mg or placebo (administered as 
two 4 mg tablets) (Cohort 5), 10 mg or placebo (Cohort 6) (administered as five 2 mg tablets), 
with the potential to escalate to 12 mg or placebo (administered as six 2 mg tablets, or three 4 mg 
tablets) with prior approval from SEC, 
Clinical Packaging & Labeling for purposes of managing blinded labeling and Clinical Supply 
Management for purposes of inventory management will remain unblinded throughout the study 
to prepare and manage the study drug. The Pharmacokinetics File Administrator, or designee, 
who facilitates data transfer of PK files between Gilead and vendors, will remain unblinded.
5.1.1.
Procedures for Breaking Treatment Codes
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject, the investigator may obtain treatment assignment directly from the IWRS system 
for that subject. Gilead recommends but does not require that the investigator contact the 
Gilead medical monitor before breaking the blind. Treatment assignment should remain blinded 
unless that knowledge is necessary to determine subject emergency medical care. The rationale 
for unblinding must be clearly explained in source documentation and on the electronic case 
report form (eCRF), along with the date on which the treatment assignment was obtained. The 
investigator is requested to contact the Gilead medical monitor promptly in case of any treatment 
unblinding.
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a 
subject’s treatment assignment is disclosed to the investigator, the subject may have study 
treatment discontinued at SEC discretion. All subjects will be followed until study completion 
unless consent to do so is specifically withdrawn by the subject.
Gilead Pharmacovigilance and Epidemiology (PVE) may independently unblind cases for 
expedited reporting of suspected unexpected serious adverse reactions (SUSARs).
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The SEC may also recommend unblinding of treatment assignments for one or more subjects to 
help determine if dosing can be resumed in subjects or cohorts where dosing has been suspended.
5.2.
Description and Handling of GS-9620 and Placebo to match
5.2.1.
Formulation
GS-9620 is available as 1 mg, 2 mg or 4 mg strength tablets. The tablets are round, biconvex, 
plain-faced, and film-coated white. Total tablet weight is 100 mg.
GS-9620 tablets contain lactose, microcrystalline cellulose, croscarmellose sodium, 
magnesium stearate, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide in 
addition to the active ingredient.
Placebo-to-match GS-9620 tablets are round, biconvex, plain-faced, and film-coated white.
Total tablet weight is 100 mg.
Placebo tablets contain lactose, microcrystalline cellulose, croscarmellose sodium, 
magnesium stearate, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.
5.2.2.
Packaging and Labeling
GS-9620 tablets and placebo-to-match GS-9620 tablets are packaged in white, high density 
polyethylene bottles. Each bottle contains 5 tablets, silica gel desiccant, and polyester packing 
material. Each bottle is capped with a child-resistant polypropylene screw cap fitted with an 
induction seal, aluminum-faced liner.
Study drug(s) to be distributed to centers in the US shall be labeled to meet applicable 
requirements of the United States Food and Drug Administration (FDA) and/or other local 
regulations.
5.3.
Dosage and Administration of GS-9620
A blinded study staff member will utilize the IWRS system to obtain bottle numbers and 
dispense blinded GS-9620 or placebo-to-match tablets from these bottles to randomized subjects 
in the planned cohorts on their dosing days. Up to six bottles of study drug (5 tablets per bottle) 
may be assigned by the IWRS for each subject at randomization.
All subjects must remain on the same formulation throughout the duration of treatment. Subjects 
will be given their dose in the clinic once every two weeks, and will not take the study 
medication with them.
5.3.1.
Fasting and food/liquids Requirement
The following fasting guidelines should be followed by subjects on all dosing days


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Table 5-1.
Fasting and food/liquids Requirement
Cohort
Fasting Period
Water/liquids Permitted
Water/liquids at Dosing
1 to 4
At least 2 hours prior to and after dosinga
1 hour prior to and 2 hours 
after dosing
240 mL of water
5, 6, 
 
Overnightb (at least 8hrs before dosing for 
Cohorts 5, 6 
 
 and at least 2 hours after dosing
1 hour prior to and 2 hours 
after dosing
240 mL of water
a
If subjects eat prior to the 2 hour fasting period before study drug dosing, no more than a light meal should be eaten 
(as described in the PK Sample Collection, Processing, Storage, and Shipment Manual).
b
If subjects did not fast overnight, plasma GS-9620 Intensive PK must not be completed. The subject should be counseled 
regarding proper fasting requirement and asked to return for the Intensive PK collection.
For Cohorts 1 to 4, GS-9620 or placebo should be taken by subjects with approximately 
240 mL of water on an empty stomach. Food will not be permitted between at least 2 hours prior 
to and until 2 hours after dosing. Aside from the 240 mL of water provided at dosing, 
water/liquids will not be permitted from 1 hour prior to until 2 hours after dosing. If subjects eat 
prior to the 2 hour fasting period before study drug dosing, no more than a light meal should be 
eaten (as described in the PK Sample Collection, Processing, Storage, and Shipment Manual).
For Cohorts 5, 6 
, GS-9620 or placebo should be administered with 
240 mL of water after an overnight fast (nothing but water for ≥ 8 hours prior to dosing).
 
 
 
[Note: For all cohorts, other than the water or cranberry juice provided with dosing, water and 
other fluids will be prohibited for 1 hour before and 2 hours after dosing.]
 
 
 
 
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5.3.3.
Storage and Handling
GS-9620 and placebo-to-match tablets should be stored at controlled room temperature of 
25 °C (77 °F); excursions are permitted between 15 °C and 30 °C (59 °F and 86 °F). Storage 
conditions are specified on the label.
Until needed for IMP dispensation to the subjects, bottles of GS-9620 and placebo-to-match 
should be stored in a securely locked area, accessible only to authorized site personnel. To 
ensure the stability of the tablets and proper product identification, the drug products should be 
stored in the containers in which they are supplied until needed. Keep the bottles tightly closed.
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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 GS-9620.
5.4.
Prior and Concomitant Medications
No clinical drug-drug interaction studies have been conducted with GS-9620. GS-9620 is 
predominantly metabolized by CYP3A with minor contribution of CYP2C8 and CYP2D6 in 
vitro, and was shown to be a substrate of P-gp and BCRP in vitro. GS-9620 plasma exposure 
may increase or decrease on co-administration with CYP3A/P-gp/BCRP inhibitors or inducers. 
ARV agents known to inhibit or induce CYP3A/P-gp/BCRP are excluded from use in this 
protocol. The following agents are NOT allowed as part of the current ARV regimen: HIV 
protease inhibitors (including low dose ritonavir), cobicistat-containing regimens, elvitegravir, 
efavirenz, etravirine, and nevirapine.
Concomitant use of herbal/natural supplements with GS-9620 may result in pharmacokinetic 
interactions resulting in alterations in exposure of GS-9620. Administration of GS-9620 with 
grapefruit juice or Seville orange juice may result in higher exposures to GS-9620. Subjects will 
refrain from consumption of grapefruit juice, grapefruits, and Seville orange juice throughout
participation in the study.
Subjects are restricted from receiving therapy with any medication listed in Table 5-3. 
Administration of any of the disallowed medications listed in Table 5-3 must be discontinued at 
least 14 days prior to the Baseline/Day 1 visit and through completion of treatment or the 
Early Study Drug Discontinuation Visit. Any medications not on the list must be reviewed 
with the Sponsor prior to randomization and during the study treatment period. Vitamins 
and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications are 
exceptions and are allowed during the study period. No immunomodulatory concomitant 
medications are allowed for at least 30 days prior to Pre-Baseline/Day -13.
Subjects’ ARV regimens must be used in accordance with their Prescribing Information.
At clinically achieved plasma concentrations, GS-9620 is not expected to be a perpetrator of 
systemic drug-drug interactions. GS-9620 concentrations estimated to be achieved in the gut at 
the ≥10 mg GS-9620 doses may transiently inhibit intestinal P-gp and increase systemic 
exposures of the drugs that are known P-gp substrates. It is recommended that oral P-gp 
substrates are administered with caution in combination with GS-9620 ≥10 mg doses.


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Table 5-3.
Prohibited Concomitant Medications
Drug Class
Agents Disallowed
Use Discouraged and To be Used 
with Caution
Acid Reducing Agents
Proton Pump Inhibitors
H2-receptor antagonistsa
ACAT inhibitor
Avasimibe
ACE Inhibitors
Captopril
Analeptic
Modafinil
Angiotensin II inhibitors
Telmisartan
Anti-anginals
Ranolazine
Anti-arrhythmics
Amiodarone, Dronedarone, Quinidine
Antibiotics
Azithromycin, Clarithromycin, Erythromycin, 
Nafcillin, Telithromycin
Ciprofloxacin, Trimethoprim
Anticonvulsants
Carbamazepine, Phenytoin, Phenobarbital, 
Oxcarbazepine
Antidepressants
Nefazodone, Venlafaxine, Ziprasidone, 
Paroxetine
Antidiabetics
Pioglitazone
Anti-epileptics
Divalproex
Antiemetics
Aprepitant, Casopitant
Antifungals
Caspofungin, Ketoconazole, Itraconazole, 
Voriconazole, Posaconazole, Fluconazole
Antimycobacterials
Rifampin, Rifampentine, Rifabutin, Isoniazid
Antiretroviral Agents
HIV Protease Inhibitors (including low dose 
Ritonavir), Cobicistat-containing regimens, 
Elvitegravir, Efavirenz, Etravirine and 
Nevirapine
Beta-Blockers
Carvedilol, Talinolol
Calcium Channel Blockers
Diltiazem, Felodipine Mibefradil, Nicardipine, 
Nifedipine, Nitrendipine, Verapamil
Diuretics
Conivaptan
Endothelin Receptor Antagonists
Bosentan
Herbal/Natural Supplements*
St. John’s Wort, Echinacea, Gingko, Milk 
thistle, Chinese herb shosaiko-to 
(or Xiao-Shai-Hu-Tang)
HMG-Coa Reductase Inhibitors
Atorvastatin
Pitavastatin, Pravastatin, 
Rosuvastatin, Lovastatin, Fluvastatin, 
Simvastatin
Immunosuppressants
Cyclosporine, Rapamycin, Sirolimus, 
Tacrolimus
Systemic Corticosteroids
All agents, including dexamethasone
Use of Prednisone as a steroid burst 
(≤ 1 week of use) should be 
monitored appropriately
Systemic Chemotherapeutic 
(antineoplastic) Agents
All agents
a
Dose not to exceed 20 mg famotidine or equivalent and dose should be administered not less than 24 hours prior to dosing 
with GS-9620 and not less than 12 hours after dosing with GS-9620.
*
Use of complementary or alternative medicines is prohibited at least 14 days prior to Baseline (Day 1) through the end of the 
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Should subjects have a need to initiate treatment with any concomitant medication, the 
Gilead Medical Monitor must be consulted prior to initiation of the new medication. In instances 
where a medication is initiated prior to discussion with the Sponsor, the Investigator must notify 
Gilead as soon as he/she is aware of the use of the medication.
5.5.
Accountability for GS-9620
The investigator is responsible for ensuring adequate accountability of all used and unused study 
drug. This includes acknowledgement of receipt of each shipment of study drug
(quantity and condition).
GS-9620 accountability records will be provided to each study site to:

Record the date received and quantity of study drug bottles

Record the date, subject number, subject initials, the study drug bottle number the pills were 
dispensed from.

Record the date, quantity of used and unused study drug returned or destroyed, along with 
the initials of the person recording the information.
5.5.1.
Investigational Medicinal Product Return or Disposal
Gilead recommends that used and unused IMP supplies be returned to the shipping facility from 
which it came for eventual destruction. The study monitor will provide instructions for return. If 
return is not possible, the study monitor will evaluate each study center’s IMP disposal 
procedures and provide appropriate instruction for destruction of unused IMP supplies. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused IMP supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for central files. 
If IMP is destroyed on site, the investigator must maintain accurate records for all IMP 
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the IMP. Upon study completion, copies of the 
IMP accountability records must be filed at the site. Another copy will be returned to Gilead. If 
drug is destroyed on site, the investigator must maintain accurate records for all study drug
bottles destroyed. Records must show the identification and quantity of each unit destroyed, the 
method of destruction, and person who disposed of the drug. All study drug records must be 
maintained at the site and copies must be submitted to Gilead Sciences at the end of the study.
The study monitor will review IMP supplies and associated records at periodic intervals.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows.
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the investigator to ensure that subjects are eligible to participate in the 
study prior to enrollment. Each study candidate must sign an Informed Consent Form prior to the 
conduct of any screening procedures, in accordance with regulatory and local 
Institutional Review Board requirements. Once consent has been obtained, all screening tests and 
procedures have been completed, and study eligibility has been confirmed, subjects will be 
randomized using an IWRS. Subjects will receive study drug within their assigned treatment 
group as described in Section 5.1. With Gilead Medical Monitor approval, candidates who fail to 
meet eligibility criteria by screening evaluations may be re-screened if there is a reasonable 
expectation that the candidate will be eligible after repeat screening. The Medical Monitor must 
approve all re-screening requests.
Retests of screening labs are permitted only if there is reason to believe the retest value will be 
within accepted parameters, if the initial value was either due to a sample processing error or due 
to an extenuating circumstance (e.g. intercurrent infection). Reasons for any re-tests should be 
documented.
6.2.
Pretreatment Assessments Screening Visit (all cohorts)
Subjects will be screened within 35 days before randomization to determine eligibility for 
participation in the study. The following will be performed and documented at screening:
6.2.1.1.
Obtain written informed consent
6.2.1.2.
Obtain medical history including history of HIV-1 disease-related events and 
prior medications within 35 days of the screening visit
6.2.1.2.1.
Collect ARV history for at least 12 months 
6.2.1.2.2.
Collect pre-ARV viral set point, pre-ARV CD4 nadir and historical genotype(s), 
if available
6.2.1.3.
Complete physical examination including vital signs (blood pressure, pulse, 
respiration rate and temperature), body weight, and height. Urogenital/anorectal 
exams will be performed at the discretion of the Investigator
6.2.1.4.
12-lead ECG performed supine
6.2.1.5.
Obtain urine collection for urinalysis


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6.2.1.6.
Obtain blood samples for:
6.2.1.6.1.
Serum pregnancy test (females of childbearing potential only). If the test is 
positive, the subject will not be enrolled
6.2.1.6.2.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, 
uric acid
6.2.1.6.3.
Estimated GFR ≥ 60 mL/min according to the Cockcroft-Gault formula for 
creatinine clearance:
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
6.2.1.6.4.
Hematology profile: complete blood count (CBC) with differential and platelet 
count
6.2.1.6.5.
CD4+ cell count
6.2.1.6.5.1.
CD8+ cell count, CD4/CD8 ratio and CD4 % (for Cohorts 5 to 9 only)
6.2.1.6.6.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.2.1.6.7.
Hepatitis B virus surface antigen serology 
6.2.1.6.8.
Hepatitis C virus serology
6.2.1.6.9.
Plasma ART trough PK (for Cohorts 5 to 9 only)
6.2.1.7.
Record any serious adverse events and all adverse events related to protocol 
mandated procedures occurring after signing of the consent form.
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 35 days after the screening visit for the Pre-Baseline/Day -13 study visit.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events electronic case report form 
(eCRF). All other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. 
See Section 7 Adverse Events and Toxicity Management for additional details.


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Protocol GS-US-382-1450
Final
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Amendment 7
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16 January 2019
6.2.2.
Pre-Baseline/Day -13 Assessments (all Cohorts)
The following evaluations are to be completed at the Pre-Baseline/Day -13 visit. The 
Pre-Baseline/Day -13 visit is to be completed within ± 3 days of the protocol specified visit date.
6.2.2.1.
Review of Inclusion/Exclusion criteria to confirm subject eligibility
6.2.2.2.
Review of AEs and changes in concomitant medications
6.2.2.3.
Review medical history
6.2.2.4.
Symptom-directed physical examination as needed
6.2.2.5.
Blood sample collection for the following laboratory analyses:
6.2.2.5.1.
PBMC for HIV specific T cell response by ELISPOT
 
 
6.2.2.5.2.
TLR7 genotyping
6.2.2.5.3.
Pharmacokinetic Blood Collection - Details of pharmacokinetic blood sampling 
procedures and sample management for all PK samples in the study will be 
documented in the Pharmacokinetic Sample Collection, Processing, Storage, and 
Shipment Manual.
6.2.2.5.3.1.
Pharmacokinetic assessments (for Cohorts 1 to 3 only) - Plasma ARV 
concentrations: a single trough PK sample will be collected. The timing of the 
ARV trough collection is to be 20-24 hours following the subject’s previous QD 
regimen dose (and, for any subject on a regimen containing a BID component, the 
trough collection must also occur 8-12 hours following the subject’s previous 
dose of that BID component).
6.2.2.5.5.
HIV specific polyfunctional T cell ICS (for Cohorts 4 to 9). 
 
 
6.2.2.5.6.
HIV-1 reservoir measurements (for Cohorts 4 to 9). 
 
 
6.2.2.5.7.
Blood sample collection for future biomarker and virology studies (for Cohorts 4
to 9).
 
CCI
CCI
CCI
CCI


GS-9620
Protocol GS-US-382-1450
Final
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Amendment 7
CONFIDENTIAL
Page 54
16 January 2019
6.2.2.6.
Obtain subject number and randomize the subject via IWRS. The subject number 
assignment and randomization may be performed up to 3 days prior to the 
in-clinic Pre-Baseline/Day -13 visit provided that all screening procedures have 
been completed and subject eligibility has been confirmed.
6.2.2.7.
Subjects should be reminded to come in for Day 1 visit in an overnight fasted 
state for Cohorts 5 to 9. 
6.2.3.
Baseline/Day 1 Assessments (all Cohorts)
Subjects are to arrive in a fasting state for the Baseline/Day 1 visit. Initiation of the treatment 
with the study drug must take place in the clinic and will be administered by blinded study staff.
Fasting requirement and food/liquids consumption requirement is shown in Table 5-1.
For all cohorts, subjects will remain on-site for 12 hours after the first dose for safety 
assessments and phlebotomy. The following evaluations are to be completed at the 
Baseline/Day 1 Visit:
6.2.3.1.
Review medical history
6.2.3.2.
Review of AEs and changes in concomitant medication
 
 
6.2.3.4.
Symptom-directed physical examination as needed
6.2.3.5.
Vital signs (blood pressure, pulse, respiration rate and temperature)
6.2.3.6.
Weight
6.2.3.7.
VAS Adherence Questionnaire to be completed by the subject. Subject is to read 
questionnaire by himself/herself and write/mark answers directly onto 
questionnaires. (Cohorts 5 to 9 only)
6.2.3.8.
Urine collection for the following laboratory procedures:
6.2.3.8.1.
Urinalysis 
6.2.3.8.2.
Urine pregnancy test (females of childbearing potential only). If the urine 
pregnancy test is positive at Baseline/Day 1, study drug will not be dispensed. 
The positive result will be confirmed with a serum pregnancy test. If the serum 
pregnancy test is positive, the subject will not be able to participate
CCI-


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Protocol GS-US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 55
16 January 2019
6.2.3.9.
Blood sample collection for the following laboratory analyses:
6.2.3.9.1.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, 
uric acid
6.2.3.9.2.
Estimated glomerular filtration rate according to the Cockcroft-Gault formula for 
creatinine clearance
6.2.3.9.3.
Hematology profile: complete blood count (CBC) with differential and platelet 
count
6.2.3.9.4.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.2.3.9.5.
CD4+ cell count
6.2.3.9.5.1
CD8+ cell count, CD4/CD8 ratio and CD4 % (Cohorts 5 to 9 only)
6.2.3.9.6.
Serum for cytokine/soluble biomarker studies
6.2.3.9.7.
Whole blood ISG mRNA panel
6.2.3.9.8.
Cell-associated HIV-1 RNA/DNA (CAVR/CAVD) with stored PBMC.
6.2.3.9.9.
Plasma HIV-1 RNA Single Copy Assay with stored plasma 
6.2.3.9.10.
Whole blood for immune cell activation (T, B, NK) and FoxP3+Treg level
6.2.3.9.11.
PBMC intracellular cytokine staining (ICS) for Treg cells (for Cohorts 1 to 
3 only)
6.2.3.9.12.
Pharmacokinetic Blood Collection
Intensive PK sampling will occur at the following time points

Pre-dose (≤5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 12 hours post dose at 
Baseline/Day 1;

Then one sample on Day 3 at time = 48 hours post dose.
Details of pharmacokinetic blood sampling procedures and sample management for all PK 
samples in the study will be documented in the Pharmacokinetic Sample Collection, Processing, 
Storage, and Shipment Manual.


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Protocol GS-US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
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6.2.3.10.
Stool sample collection before dosing for microbiome analysis (if subject is able 
to provide) (Cohorts 5 to 9).
 
6.2.3.11.
In-Clinic Dosing

Dose GS-9620 or placebo with 240 mL of water (All Cohorts,
6.3.
Treatment Assessments (Cohorts 1 to 3)
6.3.1.
Treatment Assessments on Non Dosing Days 3, 5, 11, 17, 19, 25, 31, 33, 39, 45,
47, 53, 59, 61, 67, 73, 75 and 81
All study visits are to be scheduled relative to the Baseline/Day 1 visit. All study visits listed
above except for Day 3 allow a visit window within ± 1 day of the protocol specified visit date. 
The following procedures will be performed:
6.3.1.1.
Review of AEs and changes in concomitant medications
6.3.1.2.
Symptom-directed physical examination as needed
6.3.1.3.
Blood sample collection for the following laboratory analyses:
6.3.1.3.1.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.3.1.3.2.
Hematology profile: complete blood count (CBC) with differential and 
platelet count (Days 3, 17, 31, 45, 59 and 73 only)
6.3.1.3.3.
CD4+ cell count (Days 3, 17, 31, 45, 59 and 73 only)
6.3.1.3.4.
Serum for cytokine/soluble biomarker studies (Days 3, 17, 31, 45, 59 and 
73 only)
6.3.1.3.5.
Whole blood ISG mRNA panel (Days 3, 17, 31, 45, 59 and 73 only)
6.3.1.3.6.
Cell-associated HIV-1 RNA/DNA with stored PBMC (Days 3, 45, and 73 only)
6.3.1.3.7.
Plasma HIV-1 RNA Single Copy Assay with stored plasma (Days 3, 45, and
73 only)
CCI
CCI
CCII 
I 


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Protocol GS-US-382-1450
Final
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Amendment 7
CONFIDENTIAL
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16 January 2019
6.3.1.3.8.
Whole blood for immune cell activation (T, B, NK) (Days 3, 31 and 73 only)
6.3.1.3.9.
PBMC Intracellular cytokine staining (ICS) for Treg cells (Days 3 and 73 only)
6.3.1.3.10.
GS-9620 plasma pharmacokinetic assessment (Day 3 only)
6.3.2.
Treatment Assessments on Non Dosing Days 8, 22, 36, 50, 64 and 78
All study visits are to be scheduled relative to the Baseline/Day 1 visit. Study visits on 
Days 8, 22, 36, 50, 64 and 78 are to be completed within ± 1 day of the protocol specified visit 
date. The following procedures will be performed:
6.3.2.1.
Review of AEs and changes in concomitant medications
6.3.2.2.
Symptom-directed physical examination as needed
6.3.2.3.
Urine collection for urinalysis
6.3.2.4.
Blood sample collection for the following laboratory analyses:
6.3.2.4.1.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium,
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, 
uric acid
6.3.2.4.2.
Hematology profile: complete blood count (CBC) with differential and 
platelet count
6.3.2.4.3.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.3.2.4.4.
CD4+ cell count
6.3.2.4.5.
Serum for cytokine/soluble biomarker studies
6.3.2.4.6.
Whole blood ISG mRNA panel
6.3.3.
Treatment Assessments on Dosing Days 15, 29, 43, 57 and 71
On dosing days, GS-9620 or placebo should be taken by subject with approximately 240 mL of 
water on an empty stomach. Food will not be permitted between at least 2 hours prior to and 
until 2 hours after dosing. Aside from the 240 mL of water provided at dosing, water/liquids will 
not be permitted from 1 hour prior to until 2 hours after dosing. If subjects eat prior to the 2 hour 
fasting period before study drug dosing, no more than a light meal should be eaten
(as described in the PK Sample Collection, Processing, Storage, and Shipment Manual).
These fasting guidelines should be followed by subjects on all dosing days.


GS-9620
Protocol GS-US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
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16 January 2019
Prior to the subject being administered the in-clinic dose the Investigator must verify the 
subject’s continued eligibility for in-clinic dosing, including the absence of Dose Limiting 
Toxicities (DLTs) described in Section 7.6.1.
All doses will be directly administered to the study subject by blinded site staff.
6.3.3.1.
Review of AEs and changes in concomitant medication
6.3.3.2.
Symptom-directed physical examination as needed
6.3.3.3.
Vital signs (blood pressure, pulse, respiration rate and temperature)
6.3.3.4.
Urine collection for the following laboratory procedures:
6.3.3.4.1.
Urinalysis 
6.3.3.4.2.
Urine pregnancy test (females of childbearing potential only). If the urine 
pregnancy test is positive at a dosing visit, study drug will not be dispensed. The 
positive result will be confirmed with a serum pregnancy test. If the serum 
pregnancy test is positive, the subject will be discontinued from the study
6.3.3.5.
Blood sample collection for the following laboratory analyses:
6.3.3.5.1.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, 
uric acid
6.3.3.5.2.
Hematology profile: complete blood count (CBC) with differential and 
platelet count
6.3.3.5.3.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.3.3.5.4.
CD4+ cell count
6.3.3.5.5.
Cell-associated HIV-1 RNA/DNA with stored PBMC (Days 43 and 71 only)
6.3.3.5.6.
Serum for cytokine/soluble biomarker studies collected pre-dose
6.3.3.5.7.
Whole blood ISG mRNA panel collected pre-dose
6.3.3.5.8.
Plasma HIV-1 RNA Single Copy Assay with stored plasma collected pre-dose 
(Days 43 and 71 only)
6.3.3.5.9.
Whole blood for immune cell activation (T, B, NK,) and FoxP3+Treg level 
collected pre-dose (Days 29 and 71 only)


GS-9620
Protocol GS-US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 59
16 January 2019
6.3.3.5.10.
PBMC for ELISPOT collected pre-dose (Day 71 only)
6.3.3.5.11
PBMC Intracellular cytokine staining (ICS) for Treg cells (Day 71 only)
6.3.3.6.
The Investigator will verify the subject’s continued eligibility for in-clinic dosing, 
including the absence of DLTs described in Section 7.6.1.
6.3.3.7.
In-Clinic Dosing
6.4.
Treatment Assessments (Cohorts 4 to 9)
 
6.4.1.
Treatment Assessments on Non Dosing Days 2, 58 and 128
All study visits are to be scheduled relative to the Baseline/Day 1 visit. The following procedures 
will be performed:
6.4.1.1.
Review of AEs and changes in concomitant medications 
6.4.1.2.
Symptom-directed physical examination as needed
6.4.1.3.
Urine collection for urinalysis (Day 2 only)
6.4.1.4.
Blood sample collection for the following laboratory analyses:
6.4.1.4.2.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, 
uric acid (Day 2 only)
6.4.1.4.3.
Hematology profile: complete blood count (CBC) with differential and platelet 
count (Day 2 only)
6.4.1.4.4.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.4.1.4.5.
Serum for cytokine/soluble biomarker studies
6.4.1.4.6.
Whole blood ISG mRNA panel
6.4.1.4.7.
Whole blood for immune cell activation (T, B, NK) 
CCI


GS-9620
Protocol GS-US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 60
16 January 2019
6.4.2.
Treatment Assessments on Non Dosing Days 3, 59 and 129
All study visits are to be scheduled relative to the Baseline/Day 1 visit. The following procedures 
will be performed:
6.4.2.1.
Review of AEs and changes in concomitant medications 
6.4.2.2.
Symptom-directed physical examination as needed
6.4.2.3.
Urine collection for urinalysis (Days 59 and 129 only)
6.4.2.4.
Blood sample collection for the following laboratory analyses:
6.4.2.4.1.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium,
uric acid (Days 59 and 129 only)
6.4.2.4.2.
Hematology profile: complete blood count (CBC) with differential and platelet 
count (Days 59 and 129 only)
6.4.2.4.3.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.4.2.4.4.
Serum for cytokine/soluble biomarker studies
6.4.2.4.5.
Whole blood ISG mRNA panel 
6.4.2.4.6.
Cell-associated HIV-1 RNA/DNA with stored PBMC 
6.4.2.4.7.
Plasma HIV-1 RNA Single Copy Assay with stored plasma 
6.4.2.4.8.
Whole blood for immune cell activation (T, B, NK) 
6.4.2.4.9.
GS-9620 plasma pharmacokinetic assessment (Day 3 only)
6.4.3.
Treatment Assessments on Non Dosing Days 8, 22, 36, 50, 64, 78, 92, 106, 120 
and 134
All study visits are to be scheduled relative to the Baseline/Day 1 visit. Study visits on 
Days 8, 22, 36, 50, 64, 78, 92, 106, 120 and 134 are to be completed within ± 1 day of the 
protocol specified visit date. The following procedures will be performed:
6.4.3.1.
Review of AEs and changes in concomitant medications
6.4.3.2.
Symptom-directed physical examination as needed
6.4.3.3.
Urine collection for urinalysis (Days 50, 64, 78, 92, 120 and 134 only)


GS-9620
Protocol GS-US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 61
16 January 2019
6.4.3.4.
Blood sample collection for the following laboratory analyses:
6.4.3.4.1.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium,
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, 
uric acid (Days 50, 64, 78, 92, 120 and 134 only)
6.4.3.4.2.
Hematology profile: complete blood count (CBC) with differential and 
platelet count (Days 50, 64, 78, 92, 120 and 134 only)
6.4.3.4.3.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.4.3.4.4.
CD4+ cell count (Days 50, 64, 78, 92, 120 and 134)
6.4.3.4.4.1
CD8+ cell count, CD4/CD8 ratio and CD4 % (Days 50, 64, 78, 92, 120 and 134 
for Cohorts 5 to 9 only)
6.4.3.4.5.
Serum for cytokine/soluble biomarker studies (Days 50, 64 and 134 only)
6.4.3.4.6.
Whole blood ISG mRNA panel (Days 50, 64 and 134 only)
6.4.4.
Treatment Assessments on Dosing Days 15, 29, 43, 57, 71, 85, 99, 113 and 127
Subjects are to arrive in a fasting state for the Dosing Days 15, 29, 43, 57, 71, 85, 99, 113 and 
127 and to follow fasting and food/liquids consumption requirement shown in 1. Initiation of the 
treatment with the study drug must take place in the clinic and will be administered by blinded
study staff.
For all subjects in Cohort 6, Dose 4 (Day 43) will occur after SEC review has been completed. 
Prior to the subject being administered the in-clinic dose the Investigator must verify the 
subject’s continued eligibility for in-clinic dosing, including the absence of Dose Limiting 
Toxicities (DLTs) described in Section 7.6.1.
All doses will be directly administered to the study subject by blinded site staff.
6.4.4.1.
Review of AEs and changes in concomitant medication
6.4.4.2.
Symptom-directed physical examination as needed
6.4.4.3.
Vital signs (blood pressure, pulse, respiration rate and temperature)
6.4.4.4.
Observe, if possible, and record the exact time that subject starts consuming the 
meal, the time that (s)he finishes the meal, and what (if anything) is not eaten and 
how much is consumed (Cohort 9 only)


GS-9620
Protocol GS-US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 62
16 January 2019
6.4.4.5.
VAS Adherence Questionnaire to be completed by the subject. Subject is to read 
questionnaire by himself/herself and write/mark answers directly onto 
questionnaires. (Days 29, 57, 99 and 127 for Cohorts 5 to 9 only)
6.4.4.6.
Urine collection for the following laboratory procedures:
6.4.4.6.1.
Urinalysis 
6.4.4.6.2.
Urine pregnancy test (females of childbearing potential only). If the urine 
pregnancy test is positive at a dosing visit, study drug will not be dispensed. The 
positive result will be confirmed with a serum pregnancy test. If the serum 
pregnancy test is positive, the subject will be discontinued from the study
6.4.4.7.
Blood sample collection for the following laboratory analyses:
6.4.4.7.1
Plasma ART trough PK (Days 29, 57, 85 and 99 for Cohort 5; Days 57 and 99
for Cohorts 6 
6.4.4.7.2.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, 
uric acid
6.4.4.7.3.
Hematology profile: complete blood count (CBC) with differential and 
platelet count
6.4.4.7.4.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.4.4.7.5.
CD4+ cell count
6.4.4.7.5.1
CD8+ cell count, CD4/CD8 ratio and CD4 % (Cohorts 5 to 9 only)
6.4.4.7.6.
Cell-associated HIV-1 RNA/DNA (CAVR/CAVD) with stored PBMC (Days 57 
and 127 only)
6.4.4.7.7.
Serum for cytokine/soluble biomarker studies collected pre-dose (Day 43 for
Cohort 6 subjects who receive 12 mg at Dose 4; Days 57 and 127 for all subjects)
6.4.4.7.8.
Whole blood ISG mRNA panel collected pre-dose (Day 43 for Cohort 6 subjects
who receive 12 mg at Dose 4; Days 57 and 127 for all subjects)
6.4.4.7.9.
Plasma HIV-1 RNA Single Copy Assay with stored plasma collected pre-dose 
(Days 57 and 127 only)
6.4.4.7.10.
Whole blood for immune cell activation (T, B, NK,) and FoxP3+Treg level 
collected pre-dose (Days 57 and 127 only)
CCI-


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Protocol GS-US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 63
16 January 2019
6.4.4.7.11.
Pharmacokinetic Blood Collection (only if the SEC approves the dose 
escalation to 12 mg in Cohort 6, starting from Dose 4 and onwards) 
Intensive PK sampling will occur at the following time points

Pre-dose (≤5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 12 hours post dose at Day 43;

Then one sample on Day 45 (48 hours post dose)
Details of pharmacokinetic blood sampling procedures and sample management for all PK 
samples in the study will be documented in the Pharmacokinetic Sample Collection, Processing, 
Storage, and Shipment Manual. 
6.4.4.8.
The Investigator will verify the subject’s continued eligibility for in-clinic dosing, 
including the absence of DLTs described in Section 7.6.1.
6.4.4.9.
In-Clinic Dosing
6.4.5.
Treatment Assessments on Non Dosing Days 31, 45, 73, 87, 101 and 115 
(For Cohorts 5 to 9 only)
All study visits are to be scheduled relative to the Baseline/Day 1 visit. Study visits on Day 31, 
Day 45, Day 73, Day 87, Day 101 and Day 115 Day are to be completed within ± 1 day of the 
protocol specified visit date. The following procedures will be performed:
6.4.5.1.
Review of AEs and changes in concomitant medication
6.4.5.2.
Symptom-directed physical examination as needed
6.4.5.3.
Urine collection for urinalysis (Days 73, 87, 101 and 115 only)
6.4.5.4.
Blood sample collection for the following laboratory analyses:
6.4.5.4.1.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric 
acid (Days 73, 87, 101 and 115 only)
6.4.5.4.2.
Hematology profile: complete blood count (CBC) with differential and platelet 
count (Days 73, 87, 101 and 115 only)
6.4.5.4.3.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.4.5.4.4.
Serum for cytokine/soluble biomarker studies (Day 45, only if the SEC approves 
the dose escalation to 12 mg in Cohort 6 starting from Dose 4)
6.4.5.4.5.
Whole blood ISG mRNA panel (Day 45, only if the SEC approves the dose 
escalation to 12 mg in Cohort 6 starting from Dose 4)


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Protocol GS-US-382-1450
Final
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Amendment 7
CONFIDENTIAL
Page 64
16 January 2019
6.5.
Post-treatment Assessments
6.5.1.
End of Study Visit (all Cohorts)
30 days after the last administration of study drug, subjects will return to the study center to 
complete an end of study visit. For the purpose of scheduling the end of study visit, a ± 3 days 
window may be used. The following evaluations and/or procedures will be performed at the 
end of study visit for all cohorts, unless otherwise specified:
6.5.1.1.
Review of AEs and changes in concomitant medication
6.5.1.2.
Symptom-directed physical examination as needed
6.5.1.3.
Weight
6.5.1.4.
Urine collection for the following laboratory procedures:
6.5.1.4.1.
Urinalysis 
6.5.1.4.2.
Urine pregnancy test (females of childbearing potential only, if not done within 
the previous 30 days). 
6.5.1.5.
Stool sample collection for microbiome analysis (if subject is able to provide) 
(Cohorts 5 to 9 only). 
 
6.5.1.6.
Blood sample collection for the following laboratory analyses:
6.5.1.6.1.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, 
uric acid
6.5.1.6.2.
Estimated glomerular filtration rate according to the Cockcroft-Gault formula for 
creatinine clearance
6.5.1.6.3.
Hematology profile: complete blood count (CBC) with differential and 
platelet count
6.5.1.6.4.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.5.1.6.5.
CD4+ cell count
6.5.1.6.5.1
CD8+ cell count, CD4/CD8 ratio and CD4 % (Cohorts 5 to 9 only)
6.5.1.6.6.
Cell-associated HIV-1 RNA/DNA (CAVR/CAVD) with stored PBMC 
CCI


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Protocol GS-US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 65
16 January 2019
6.5.1.6.7.
Plasma HIV-1 RNA Single Copy Assay with stored plasma 
6.5.1.6.8.
PBMC for HIV specific T cell response by ELISPOT
 
 
6.5.1.6.9.
Serum for cytokine/soluble biomarker studies (Cohorts 1 to 3 only)
6.5.1.6.10.
Whole blood ISG mRNA panel (Cohorts 1 to 3 only)
6.5.1.6.11.
HIV specific poly-functional T cell ICS (Cohorts 4 to 9). 
 
 
6.5.1.6.12.
HIV reservoir measurements (Cohorts 4 to 9).
 
 
6.5.1.6.13.
 
6.5.2.
Early Study Drug Discontinuation Visit (all Cohorts)
Subjects who prematurely discontinue study drug will be required to complete an Early Study 
Drug Discontinuation Visit (ESDD) within 30 days after their last dose of study treatment.
If a subject discontinues study dosing (for example, as a result of an AE) every attempt should be 
made to keep the subject in the study and continue to perform the required study-related 
follow-up and procedures.
At the ESDD Visit, any evaluations showing abnormal results indicating that there is a 
possible or probable causal relationship with the study drug, should be repeated weekly 
(or as often as deemed prudent by the Investigator) until the abnormality is resolved, 
returns to baseline, or is otherwise explained.
The following evaluations are to be completed at the Early Study Drug Discontinuation Visit for 
all cohorts, unless otherwise specified:
6.5.2.1.
Review of AEs and changes in concomitant medication
6.5.2.2.
Symptom-directed physical examination as needed
6.5.2.3.
Weight
CCI
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6.5.2.4.
Urine collection for the following laboratory procedures:
6.5.2.4.1.
Urinalysis 
6.5.2.4.2.
Urine pregnancy test (females of childbearing potential only). 
6.5.2.5.
Stool sample for microbiome analysis (if subject is able to provide) 
(Cohorts 5 to 9). 
 
 
6.5.2.6.
Blood sample collection for the following laboratory analyses:
6.5.2.6.1.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, 
uric acid
6.5.2.6.2.
Estimated glomerular filtration rate according to the Cockcroft-Gault formula for 
creatinine clearance
6.5.2.6.3.
Hematology profile: complete blood count (CBC) with differential and 
platelet count
6.5.2.6.4.
Plasma HIV-1 RNA (TaqMan® v2.0)
6.5.2.6.5.
CD4+ cell count
6.5.2.6.5.1
CD8+ cell count, CD4/CD8 ratio and CD4 % (Cohorts 5 to 9 only)
6.5.2.6.6.
Serum for cytokine/soluble biomarker studies
6.5.2.6.7.
Whole blood ISG mRNA panel
6.6.
Criteria for Discontinuation of Study Treatment
Study medication may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree 

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific treatment and/or procedures or is considered to not be in the 
subject’s best interest

Subject receives GS-9620 and experiences one or more DLTs (at discretion of SEC)
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
Subject request to discontinue for any reason

Subject noncompliance

Pregnancy during the study; refer to Appendix 5

Discontinuation of the study at the request of Gilead, a regulatory agency or an 
institutional review board (IRB)
 
 
 
 
 
 
 
6.8.
Prolonged Viremia
Subjects will be considered to have prolonged viremia if they have two consecutive plasma 
HIV-1 RNA levels ≥200 copies/mL during a single dosing period.
6.8.1.
Management of Prolonged Viremia
If plasma HIV-1 RNA level is ≥200 copies/mL at any visit post-dose, viral load will be tested at 
next scheduled visit or retested within 4 days. The next dose will be withheld and only given 
after viral load of ≤200 copies/mL is achieved. The study procedure schedule will be reset 
relative to the next dose of study drug. 
If HIV-1 RNA viral load ≥200 copies/mL is confirmed during a single dosing period, then this 
subject will be considered to have prolonged viremia and blood samples from this visit will be 
used for HIV-1 genotype/phenotype testing with assays corresponding to the antiretroviral
medications the subject is taking.
If primary resistance mutations to the subject’s existing ART regimen are identified, a new ART
regimen will be configured at the discretion of the Investigator and the subject will be 
discontinued from the study. If the genotyping/phenotyping assay fails to provide results or no 
drug resistance mutations are identified, a new ART regimen may be configured at the discretion
of the Investigator. Subjects who start a new ART regimen will not be allowed to receive further
doses of study drug, but can be monitored for the study duration at the discretion of the study
Investigator. Subjects who remain on their current ART regimen must show confirmed HIV-1 
RNA levels <200 copies/mL before resuming study drug dosing at the discretion of the 
Investigator.
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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the 
treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. AEs may also include pre- or post-treatment complications that occur as a 
result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. Preexisting events that increase in severity or change in nature during or 
as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion. 
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (see Section 7.7.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
eCRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization


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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
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 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin).
For specific information on handling of clinical laboratory abnormalities in this study, please 
refer to Section 7.5.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to 
IMP therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the IMP. For SAEs, an 
alternative causality must be provided (eg, pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.


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It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting.
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures, (eg., venipuncture)
7.2.2.
Assessment of Severity
A distinction should be drawn between seriousness and severity of AEs. An AE that is assessed 
as Grade 4 (potentially life-threatening) should not be confused with an SAE. Severity is a 
category utilized for rating the intensity of an event; and both AEs and SAEs can be assessed as 
Grade 4. An event is defined as “serious” when it meets one of the predefined outcomes 
described above in Section 7.1.2.
Severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 4) For adverse events associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (eCRF): all serious adverse events (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 30 days after last administration of study IMP must be reported to the eCRF database as 
instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
period.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead Pharmacovigilance and Epidemiology (PVE) as instructed. This also 
includes any SAEs resulting from protocol-associated procedures performed after informed 
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Any SAEs and deaths that occur after the post treatment follow-up visit but within 4 weeks of 
the last dose of study IMP, regardless of causality, should also be reported.
Investigators are not obligated to actively seek SAEs after the protocol defined follow up period,
however, if the investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of IMP, he/she should promptly document and report 
the event to Gilead PVE.

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) Reporting Process

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead PVE within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically, ie, the eCRF 
database is not functioning, record the SAE on the paper serious adverse event reporting 
form and submit within 24 hours to Gilead PVE:
Gilead Sciences PVE Representative:
Fax:
E-mail:

As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been locked, 
no further action is necessary.

For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE form.
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7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
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.
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities are usually not recorded as AEs or SAEs. However, laboratory 
abnormalities (eg, clinical chemistry, hematology, urinalysis) independent of the 
underlying medical condition that require medical or surgical intervention or lead to 
investigational medicinal product interruption or discontinuation must be recorded as an AE, as 
well as an SAE, if applicable. In addition, laboratory or other abnormal assessments 
(eg, electrocardiogram, x-rays, vital signs) that are associated with signs and/or symptoms must 
be recorded as an AE or SAE if they meet the definition of an AE (or SAE) as described in 
Sections 7.1.1 and 7.1.2. If the laboratory abnormality is part of a syndrome, record the 
syndrome or diagnosis (ie, anemia) not the laboratory result (ie, decreased hemoglobin).
Severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 4) For adverse events associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.


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7.6.
Toxicity Management
7.6.1.
Management of Dose-Limiting Toxicities (DLTs)
Prior to the subject being administered the in-clinic dose the Investigator will verify the subjects 
continued eligibility for dosing, including the absence of DLTs listed below:

ALT elevation as defined as:
ALT ≥ 10 × ULN OR
Confirmed ALT elevation (ie. Grade shift or 2× previous value) with evidence of 
worsened hepatic function (e.g. total bilirubin > 2mg/dL above Baseline, 
serum albumin > 1 g/dL decrease from Baseline)

A confirmed ≥Grade 3 AE considered drug related by the Investigator

A confirmed, clinically significant ≥Grade 3 laboratory abnormality considered study 
drug-related by the investigator

A persistent (≥ 72 hours) ≥Grade 2 flu-like symptom (pyrexia, fatigue, myalgia, arthralgia, 
headache, chills) considered study drug-related by the investigator

A post-dose increase in plasma HIV-1 RNA that fails to resolve to < 50 copies/mL within 
10 days in Cohorts 1 to 3 

A post-dose increase in plasma HIV-1 RNA that fails to resolve to < 200 copies/mL within 
10 days in Cohorts 4 to 9
The designated Safety Evaluation Committee contact will be notified within 24 hours of the 
Investigator’s knowledge of a subject having any of the above DLTs. Dosing must be withheld 
until the Safety Evaluation Committee determines the appropriate next steps, including but not 
limited to additional safety, pharmacokinetic and pharmacodynamic assessments. The SEC may 
also suspend dosing in additional subjects or cohorts.
The SEC may hold or discontinue study drug dosing for a subject if they receive GS-9620 and 
experience one or more DLTs. The SEC may hold or discontinue study drug dosing for a cohort 
if ≥2 out of 6 subjects receiving GS-9620 experience one or more DLTs. 


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7.6.2.
Management of Other Toxicities
Unless otherwise specified in Section 7.6.1, toxicities will be managed according to the 
guidelines below.

All clinical and clinically significant laboratory toxicities will be managed according to 
uniform guidelines detailed in Appendix 3.

Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat 
testing within 3 calendar days of receipt of results and before investigational medicinal 
product (IMP) discontinuation, unless such a delay is not consistent with good medical 
practice.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the Table for GSI Grading Scale for Severity of Adverse Events and Laboratory 
Abnormalities (Appendix 4).

When restarting IMP following resolution of the adverse event, the investigational medicinal 
product should be restarted at full dose or modified dose that is dependent upon discussion 
with the Gilead Sciences Medical Monitor.

Any recurrence of the Grade 3 or 4 clinical or clinically significant laboratory adverse event 
following dose interruption mandates permanent discontinuation of IMP.

Any questions regarding toxicity management should be directed to the 
Gilead Sciences Medical Monitor.
7.6.2.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue investigational medicinal product at the discretion of the Investigator.
7.6.2.2.
Grade 3 Laboratory Abnormality or Clinical Event

For a Grade 3 clinical event or clinically significant Grade 3 laboratory abnormality 
confirmed by repeat testing, IMP should be withheld until the toxicity returns to Grade 2.

If a laboratory abnormality recurs to Grade 3 following rechallenge with IMP, then IMP
should be permanently discontinued and the subject managed according to local practice. 
7.6.2.3.
Grade 4 Laboratory Abnormality or Clinical Event

For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality 
confirmed by repeat testing, IMP should be withheld until the toxicity returns to Grade 2. 


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
For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality 
confirmed by repeat testing that is considered related to IMP, IMP should be permanently 
discontinued and the subject managed according to local practice. The subject should be 
followed as clinically indicated until the laboratory abnormality returns to baseline or is 
otherwise explained, whichever occurs first. A clinically significant Grade 4 laboratory 
abnormality that is not confirmed by repeat testing should be managed according to the 
algorithm for the new toxicity grade.
Investigational medicinal product may be continued without dose interruption for a clinically 
non-significant (and therefore not an AE), Grade 4 laboratory abnormality (eg, Grade 4 CK after 
strenuous exercise, or triglyceride elevation that is non-fasting or that can be medically 
managed).
7.7.
Special Situations Reports
7.7.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, occupational exposure with an AE, AE in 
an infant following exposure from breastfeeding 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 
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.


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7.7.2.
Instructions for Reporting Special Situations
7.7.2.1.
Instructions for Reporting Pregnancies
Subjects should be instructed to notify the investigator if they become pregnant at any time 
during the study, or if they become pregnant within 4 weeks of last study drug dose. Subjects 
who become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator, and seek the investigator’s advice regarding action required with 
study drug immediately. The investigator should counsel the subject regarding the possible 
effects of prior study drug exposure on the fetus and the need to inform the study site of the 
outcome of the pregnancy.
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study, including the post study drug follow-up
period, to Gilead PVE using the pregnancy report form within 24 hours of becoming aware of 
the pregnancy.
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
the Adverse and Serious Adverse Section 7.1.1 and 7.1.2. Furthermore, any SAE occurring as an 
adverse pregnancy outcome post study must be reported to Gilead PVE.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead PVE using the pregnancy outcome report 
form. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead PVE. Gilead PVE contact information is as follows: 
Gilead Sciences PVE Representative:
Fax:
E-mail:
PPD
PPD


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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 or Gilead PVE using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead PVE, 
fax number
 or email 
Refer to Appendix 5 for Pregnancy Precautions, Definition for Female of Childbearing Potential 
and Contraceptive Requirements.
7.7.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and
forwarded to or Gilead PVE within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications.
Special situations involving non-Gilead concomitant medications do 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 and the eCRF completion guidelines for full instructions on the mechanism of 
special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.
Special Situations reports should be sent to Gilead Sciences PVE:
Gilead Sciences PVE Representative:
Fax:
E-mail:
PPD
PPD
PPD
PPD


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary analysis objectives are:

To evaluate the safety and tolerability of escalating, multiple doses of GS-9620 in HIV-1 
infected virologically suppressed adults on ART

To evaluate the virologic effect of GS-9620 as measured by changes in plasma HIV-1 RNA.
The secondary analysis objectives are:

To evaluate the PK of GS-9620

To evaluate the PD of GS-9620 as measured by changes in ISGs and serum cytokines in 
whole blood compared to placebo

To evaluate effects of GS-9620 on whole blood immune cell activation (T cell, B cell, 
NK cell)
The exploratory analysis objectives are:
 
 
 
8.1.2.
Primary Endpoint

The primary safety endpoint is incidence of treatment-emergent SAEs and all 
treatment-emergent adverse events.

The primary virology endpoint is maximum change from baseline in plasma log10
HIV-1 RNA at any post-dose timepoint
CCII 
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8.1.3.
Secondary Endpoint
The secondary endpoints are:

Change from baseline in plasma HIV-1 RNA at post-baseline visits

Proportion of subjects with plasma HIV-1 RNA > 50 copies/mL at any post-dose timepoint
8.1.4.
Other Endpoints of Interest
Other endpoints include:

Change from baseline in the levels of serum cytokines 

Change from baseline and fold induction in mRNA for ISGs

Change from baseline in peripheral blood lymphocyte count for T/B/NK/pDC/mDC
including: CD4 and CD8 populations, CD4/CD8 ratio, CD4 % and lymphocyte activation 
(T, B and NK cells)
8.1.5.
Exploratory Endpoints
 
 
 
 
 
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All Randomized
The randomized analysis set includes all subjects who are randomized into the study. This is the 
primary analysis set for by-subject listings.
8.2.1.2.
Efficacy
8.2.1.2.1
Full Analysis Set
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The full analysis set (FAS) will include all subjects who (1) are randomized into the study and 
(2) have received at least one dose of study drug. Subjects with major eligibility violations that 
are identifiable based on pre-randomization characteristics will be excluded.
Subjects will be grouped according to the treatment to which they were randomized.
8.2.1.3.
Safety
The safety analysis set will include all randomized subjects who received at least one dose of 
study drug. All the data collected up to 30 days after subjects permanently discontinue their 
study drug will be included in the safety summaries. Subjects will be grouped according to the 
treatment they actually received.
8.2.1.4.
Phamacokinetics
8.2.1.4.1
GS-9620 Pharmacokinetic Analysis Set
The GS-9620 pharmacokinetic (PK) analysis set will include all subjects who are randomized 
and have received at least one dose of study drug and for whom PK parameters of analyte 
GS-9620 are available.
8.2.1.4.2
ARV Pharmacokinetic Analysis Set
The ARV PK analysis set will include all subjects who are randomized and have received at least 
one dose of study drug and for whom the PK concentration of any analyte of the ARV is 
available.
8.2.1.5.
Biomarkers
The biomarker analysis set will include all subjects who are randomized and have received at 
least one dose of study drug and for whom the biomarkers are available.
8.3.
Data Handling Conventions
Natural logarithm transformation for key PK parameters, such as Cmax, AUClast and AUCinf, will 
be applied for pharmacokinetic analysis, as appropriate.
PK concentration values below the limit of quantitation (BLQ) will be presented as “BLQ” in the 
concentration data listing, will be treated as zero for the determination of summary and order 
statistics, and will be excluded for natural logarithm transformation. PK parameter values that 
are BLQ will be presented as “BLQ” in the parameter data listing and will be excluded in any 
calculation of geometric means or ratios.
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline measurements will be summarized using standard descriptive 
methods by treatment group.


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Demographic summaries will include sex, race/ethnicity, and age.
Baseline data including body weight, height, body mass index, HIV-1 infection will be 
summarized.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary virology endpoint is the maximum change from baseline in plasma log10
HIV-1 RNA at any post-dose timepoint. It will be summarized by treatment group. The primary 
analysis of the efficacy will be based on the full analysis set (FAS).
8.5.2.
Secondary Analyses
The change from baseline in plasma log10 HIV-1 RNA at post-baseline visits will be summarized 
by treatment group.
The number and proportion of subjects with plasma HIV-1 RNA > 50 copies/mL at any 
post-dose timepoint will be summarized by treatment group.
8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set.
All safety data collected on or after the date that study drug was first taken up to the date of 
last dose of study drug plus 30 days will be summarized by treatment group according to the 
study drug received. Data for the pretreatment period and the period post the date of last dose of 
study drug plus 30 days will be included in data listings.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug 
administration data. Exposure data will be summarized by treatment group.
Duration of exposure to study drug will be expressed as the number of weeks between the 
first and last dose of the study drug, inclusive, regardless of temporary interruptions in study 
drug administration and summarized by treatment.
Dosing information for individual subjects will be listed.
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.
Treatment-emergent AEs are 1) any AEs with onset date on or after the study drug start date and 
no later than 30 days after the study drug stop date, or 2) any AEs leading to study drug 
discontinuation.


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Summaries (number and percentage of subjects) of treatment-emergent adverse events 
(by SOC and PT) will be provided by treatment group. Additional summaries will include 
summaries for adverse events by grade, Investigator’s assessment of relationship to study drug, 
and effect on study drug dosing.
On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Category C events that are indicative of an AIDS-Defining Diagnoses. The Gilead medical 
personnel will review the possible Category C events and approve the events that meet the 
definition. Those events that do meet the Category C definition of an AIDS-Defining Diagnosis 
will be listed.
A listing of Category C, AIDS-Defining Diagnosis can be found in Appendix 6.
8.6.3.
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 defined in Grading of 
laboratory abnormalities provided in Appendix 4.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
one toxicity grade from baseline at any time post baseline up to and including the date of 
last dose of study drug plus 30 days, will be summarized by treatment group. If baseline data are 
missing, any graded abnormality (i.e., at least a Grade 1) will be considered treatment emergent. 
The maximum toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the subject has 
been discontinued from treatment plus 30 days will be included in a data listing.
8.7.
Pharmacokinetic Analysis
The concentration data of GS-9620 and ARV (trough samples), if analyzed, will be summarized 
by nominal sampling time using descriptive statistics. For GS-9620, pharmacokinetic parameters 
(Cmax, Tmax, Clast, Tlast, λz, AUCinf, AUClast, and t½) will be listed and summarized using 
descriptive statistics (e.g., sample size, arithmetic mean, geometric mean, coefficient of variation 
(%), standard deviation, median, minimum, and maximum). Plasma concentrations over time 
will be plotted in semi-logarithmic and linear formats as mean ± standard deviation, and median 
(Q1, Q3). For ARVs, trough sample concentrations for an individual will be descriptively 
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8.8.
Sample Size
This is an exploratory study to characterize the safety and efficacy of GS-9620; therefore, 
no power calculation was performed. Sample size is determined based on empirical 
considerations. A total of up to 54 subjects receiving GS-9620 will provide reasonable 
preliminary assessment of safety.
8.9.
Safety Evaluation Committee
A Safety Evaluation Committee (SEC) will review study progress, virology and safety of 
enrolled subjects. The SEC will consist of members not directly involved with the conduct of the 
study. After all subjects in a cohort have received at least three doses (Cohorts 1 to 3, and 6) or 
five doses (Cohorts 4 and 5), the SEC will review safety data from that cohort, including adverse 
events, clinical laboratory results, and plasma HIV-1 RNA, before approving opening of 
enrollment in the next cohort. For Cohort 6, SEC will confer once all subjects have completed 
3 doses of 10 mg GS-9620, and recommend whether or not subjects may proceed with a dose 
escalation to 12 mg starting with Dose 4.
 
A cohort may be suspended if ≥2 out of 6 subjects receiving GS-9620 
experience one or more DLTs considered related to study drug. Please refer to the SEC Charter 
for additional details.
8.10.
Analysis Schedule
Interim Unblinded Analyses
Prior to the final analysis, selected individuals from Gilead will be unblinded to assess the
interim safety, virology, biomarker, and PK data of GS-9620. This group may consist of at least
one representative from Clinical Research, Biostatistics, Clinical Pharmacology, 
Pharmacovigilance/Epidemiology, Biomarkers, Clinical Virology and may include other 
personnel as necessary.
The access to individual unblinded data (safety, virology, biomarker and PK) will be limited only 
to data relevant for analysis by the function representatives and will be summarized at the group 
level for regulatory documents and external submissions without revealing individual subject 
identification to protect study blind at the subject level. This group will review data (safety, 
virology, biomarker and PK) to support development of new clinical protocols, regulatory 
documents, and conference submissions.
Final analysis
The Sponsor will conduct a final analysis of all data after the last subject in the study completes
the last visit (Day 157) or prematurely discontinues from the study.
CCI


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (ICH) guidelines, or with the laws and 
regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject. These standards are consistent with the European Union Clinical 
Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of Good Clinical Practice, as 
outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 
21 CFR, part 50, ”Protection of Human Subjects”, and 21 CFR, part 56, 
”Institutional Review Boards”.
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 
“Financial Disclosure by Clinical Investigators”, providing documentation of their financial 
interest or arrangements with Gilead, or proprietary interests in the investigational drug under 
study. This documentation must be provided prior to the investigator’s 
(and any subinvestigators’) participation in the study. The investigator and sub-investigator agree 
to notify Gilead of any change in reportable interests during the study and for 1 year following 
completion of the study. Study completion is defined as the date when the last subject completes 
the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB) Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an. The investigator will not begin any study subject activities until 
approval from the IRB has been documented and provided as a letter to the investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the any modifications made to the protocol or any accompanying material to be provided to the 
subject after initial approval, with the exception of those necessary to reduce immediate risk to 
study subjects.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must use the most current approved consent form for documenting written informed 
consent. Each informed consent (or assent as applicable) will be appropriately signed and dated 
by the subject or the subject’s legally authorized representative and the person conducting the 
consent discussion, and also by an impartial witness if required by.


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9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form or biological sample submitted to the Sponsor, or laboratory. Laboratory specimens must 
be labeled in such a way as to protect subject identity while allowing the results to be recorded to 
the proper subject. Refer to specific laboratory instructions NOTE: The investigator must keep a 
screening log showing codes, names, and addresses for all subjects screened and for all subjects 
enrolled in the trial. Subject data will be processed in accordance with all applicable regulations. 
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, eCRF, the IMP, and any other study information, remain the 
sole and exclusive property of Gilead during the conduct of the study and thereafter. This 
information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, and 
governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);

Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);

Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;


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
Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of IMP, including dates of dispensing and return;

Record of all adverse events and other safety parameters (start and end date, and including
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data. Subsequent to data entry, a study monitor will perform source data verification 
within the EDC system. Original entries as well as any changes to data fields will be stored in the 
audit trail of the system. Prior to database lock (or any interim time points as described in the 
clinical data management plan), the investigator will use his/her log in credentials to confirm that 
the forms have been reviewed, and that the entries accurately reflect the information in the 
source documents. The eCRF capture the data required per the protocol schedule of events and 
procedures. System-generated or manual queries will be issued to the investigative site staff as 
data discrepancies are identified by the monitor or internal Gilead staff, who routinely review the 
data for completeness, correctness, and consistency. The site coordinator is responsible for 
responding to the queries in a timely manner, within the system, either by confirming the data as 
correct or updating the original entry, and providing the reason for the update 
(e.g. data entry error). At the conclusion of the trial, Gilead will provide the site with a read-only 
archive copy of the data entered by that site. This archive must be stored in accordance with the 
records retention requirements outlined in Section 9.1.5.


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9.1.7.
Investigational Medicinal Product Accountability and Return
Gilead recommends that used and unused IMP supplies be returned to the shipping facility from 
which it came for eventual destruction. The study monitor will provide instructions for return. If 
return is not possible, the study monitor will evaluate each study center’s IMP disposal 
procedures and provide appropriate instruction for destruction of unused IMP supplies. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused IMP supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for central files.
If IMP is destroyed on site, the investigator must maintain accurate records for all IMP
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the IMP. Upon study completion, copies of the 
IMP accountability records must be filed at the site. Another copy will be returned to Gilead.
The study monitor will review IMP supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB in 
accordance with local requirements and receive documented approval before modifications can 
be implemented.
9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency. Gilead will 
ensure that the report meets the standards set out in the ICH Guideline for Structure and Content 
of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in certain 
cases.


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Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after the following conditions have been met:

The results of the study in their entirety have been publicly disclosed by or with the consent 
of Gilead in an abstract, manuscript, or presentation form or the study has been completed at 
all study sites for at least 2 years

The investigator will submit to Gilead any proposed publication or presentation along with 
the respective scientific journal or presentation forum at least 30 days before submission of 
the publication or presentation. 

No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).

The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, e.g. attendance at Investigator's Meetings. If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.
9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) are resolved.


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9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the investigator 
will assure that adequate consideration is given to the protection of the subjects’ interests.


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10.
REFERENCES
Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, et al. Effect of HIV 
Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med 
2016;375 (21):2037-50.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41.
European Medicines Agency (EMA). Pegasys: EPAR – Scientific Discussion: 8 August 2006. 8 
Aug, 2006.
Fosdick A, Zheng J, Pflanz S, Frey CR, Hesselgesser J, Halcomb RL, et al. Pharmacokinetic and 
Pharmacodynamic Properties of GS-9620, a Novel TLR7 Agonist, Demonstrates 
ISG Induction without Detectable Serum Interferon at Low Oral Doses. J 
Pharmacol Exp Ther 2013.
Joint United Nations Programme on HIV/AIDS (UNAIDS). Global Aids Update 2016. Available 
at: http://www.unaids.org/en/resources/documents/2016/Global-AIDS-update-
2016. 31 May. 2016.
Kubicek WG, Anderson WD, Geber WF. Effects of hypoxia on the course of induced fever in 
dogs and monkeys. Am J Physiol 1958;195 (3):601-13.
Lanford RE, Guerra B, Chavez D, Giavedoni L, Hodara VL, Brasky KM, et al. GS-9620, an Oral 
Agonist of Toll-Like Receptor-7, Induces Prolonged Suppression of Hepatitis B 
Virus in Chronically Infected Chimpanzees. Gastroenterology 2013;144 (7):1508-
17 e10.
Li JZ, Etemad B, Ahmed H, Aga E, Bosch RJ, Mellors JW, et al. The size of the expressed HIV 
reservoir predicts timing of viral rebound after treatment interruption. AIDS 
2016;30 (3):343-53.
Lim SY, Osuna CE, Hraber PT, Hesselgesser J, Gerold JM, Barnes TL, et al. TLR7 agonists 
induce transient viremia and reduce the viral reservoir in SIV-infected rhesus 
macaques on antiretroviral therapy [Research Article]. Science translational 
medicine 2018;10:eaao452.
Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. Changing patterns of 
mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. 
Lancet 1998;352 (9142):1725-30.
Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining 
Morbidity and Mortality Among Patients With Advanced Human 
Immunodeficiency Virus Infection. N Eng J Med 1998;338 (13):853-60.


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Pilaro AM, Green MD. Toxicologist's Review: Pegylated interferon-a 2b for the Treatment of 
Chronic Hepatitis C Infection (Biologics License Application # 99-1488). Clinical 
Pharmacology/Toxicology Branch, Division of Clinical Trials Design and 
Analysis, Center for Biologics Evaluation and Research. December 19. 2000.
Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, McKenna MT. Revised 
surveillance case definitions for HIV infection among adults, adolescents, and 
children aged <18 months and for HIV infection and AIDS among children aged 
18 months to <13 years--United States, 2008. MMWR Recomm Rep 2008;57 
(RR-10):1-12.
Sogaard OS, Graversen ME, Leth S, Olesen R, Brinkmann CR, Nissen SK, et al. The 
Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo. PLoS pathogens 
2015;11 (9):e1005142.
Sterne J, Hernán M, Ledergerber B, Tilling K, Weber R, Sendi P, et al. Long-term effectiveness 
of potent antiretroviral therapy in preventing AIDS and death: a prospective 
cohort study. Lancet 2005;366 (9483):378-84.
U. S. Department of Health and Human Services (DHHS), Food and Drug Administration 
(FDA), Center for Drug Evaluation and Research (CDER). Guidance for Industry. 
Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for 
Therapeutics in Adult Healthy Volunteers. Rockville, MD. July, 2005.
Vial T, Descotes J. Clinical toxicity of the interferons. Drug Saf 1994;10 (2):115-50.
Vibholm L, Schleimann MH, Hojen JF, Benfield T, Offersen R, Rasmussen K, et al. Short-
Course Toll-Like Receptor 9 Agonist Treatment Impacts Innate Immunity and 
Plasma Viremia in Individuals With Human Immunodeficiency Virus Infection. 
Clin Infect Dis 2017;64 (12):1686-95.


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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table
Appendix 3.
Management of Clinical and Laboratory Adverse Events
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines)


PPDPPD
PPD
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Protocol GS-US-382-1450 
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Amendment 7 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 1 b, Randomized, Blinded, Placebo-Controlled Dose-Escalation Study of the Safety and 
Biological Activity of GS-9620 in HIV-I Infected, Virologically Suppressed Adults 
GS-US-382-1450, Amendment 7, 16 January 2019 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
Medical Monitor 
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) 
Signanire 
Date 
Site Number 
CONFIDENTIAL 
Page 93 
16 January 2019 


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Appendix 2. 
Study Procedures Table 
Study Procedures Table i Cohorts 1 to 3 
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CONFIDENTIAL 
Page 94 
16 January 2019 


GS-9620 
Protocol GS-US-382-1450 
Gilead Sciences, Inc. 
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16 January 2019 


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16 January 2019 


GS-9620 
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Gilead Sciences, Inc. 
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CONFIDENTIAL 
Page 97 
16 January 2019 


GS-9620 
Protocol GS-US-382-1450 
Gilead Sciences, Inc. 
Study Procedures Table (Cohort 4) 
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16 January 2019 


GS-9620 
Protocol GS-US-382-1450 
Gilead Sciences, Inc. 
Study Procedm·e 
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16 January 2019 


GS-9620 
Protocol GS-US-382-1450 
Gilead Sciences, Inc. 
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Q 
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CONFIDENTIAL 
Page 100 
16 January 2019 


GS-9620 
Protocol GS-US-382-1450 
Gilead Sciences, Inc. 
Study Procedures Table (Cohorts 5 to 9)3 
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Final 
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16 January 2019 


GS-9620 
Protocol GS-US-382-1450 
Gilead Sciences, Inc. 
.. .. 
<.I 
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1 
Study Procedm·e• 
0:: 
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CD4+ cell count 
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X 
Plasma GS-9620 
Intensive PKk 
Plasma ARTPKP 
X 
TLR 7 genotyping 
Semmfor 
cytokine/soluble 
biomarker studies 
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mRNA 
CONFIDENTIAL 
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16 January 2019 


CCI
CCI
GS-9620 
Protocol GS-US-382-1450 
Gilead Sciences, Inc. 
Study Procedm·e• 
Cell associated HIV -1 
RNA/DNA 
(CA VR/CA VD) with 
stored PBMCs 
Plasma HIV-1 RNA 
Single Copy Assay 
with stored plasma 
PBMC - ELISPO'P 
Whole blood -
inunune cell activation 
Whole blood - flow 
FoxP3+Treg 
Tcell JCS; 
HIV-I Reservoir 
measurement; 
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confinn dosing can 
proceed 
In-Clinic Dosing1 
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Evaluation to be completed within 35 days prior to Pre-Baseline/Day -13 
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Subjects should be administered study dmg after Baseline/Day I visit assessments (except for post-dose intensive PK) 
CONFIDENTIAL 
Page 103 
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16 January 2019 


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 104
16 January 2019
d
Dose 4 (Cohort 6 only) cannot occur until SEC completes review of the safety data from all subjects’ first three doses (GS-9620 10 mg dose). If the GS-9620 10mg dose is 
found to be safe, Dose 4 and subsequent Doses (5-10) will escalate to GS-9620 12 mg. If dose escalation is not approved by the SEC, subjects will continue receiving 10 mg 
of GS-9620 or placebo from Doses 4 to 10
e
All study visits are to be scheduled relative to the Baseline/Day 1 visit date
f
Collect ART history for at least 12 months; Pre-ARV viral set point, pre-ARV CD4 nadir and historical genotype will be collected if available
g
Urogenital/anorectal exams may be performed at discretion of the Investigator
h
Symptom-directed physical examination as needed
j
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test at any visit. At End of Study visit, urine pregnancy test only 
performed if not done within past 30 days
k
Details of pharmacokinetic blood sampling procedures and sample management for all PK samples in the study will be documented in the Pharmacokinetic Sample 
Collection, Processing, Storage, and Shipment Manual.
l
In Cohorts 5 and 6, 
, the study drug will be administered following an overnight fast.
 
m
Cohorts 6
only
n
Cohort 6 only, if dose escalation to 12mg is approved by SEC
o
To be collected pre-dose on dosing days
p
Cohorts 6
only required at Screening, Days 57 and Days 99
CCI
CCI
CCI
CCI
CCI
I 


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 105
16 January 2019
Appendix 3.
Management of Clinical and Laboratory Adverse Events
Grade 1 
! 
May continue 
dosing at the 
discretion of the 
investigator 
Grade 2 
~----G~r_a_d_e_J ____ ~ I 
~I---..---G_r_a_d_e_4 ____ 
I 
l 
Repeat lab to 
Repeat lab to 
confirm toxicity 
confirm toxicity 
grade 
grade 
1, 
1, 
If confirmed: 
1. Withhold investigational medicinal products until Grade 2 
2. 
Restart all investigational medicinal products at full dose 
1, 
1, 
If Grade 3 or 4 recurrence is confirmed following rechallenge 
with investigational medicinal product, discontinue all 
investigational medicinal products dosing permanently 
-
If confirmed and 
possibly or probably 
related to 
investigation al 
medicinal products, 
discontinue 
investigation al 
medicinal products 
dosing permanently 
and follow at periodic 
intervals at least 
weekly until a return 
to baseline or is 
otherwise explained 


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 106
16 January 2019
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Antiviral Toxicity Grading Scale Version: 01 April 2015
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


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 107
16 January 2019
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Neutrophil Count 
(ANC)
Adult and Pediatric, 
≥ 7 Months# 
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
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
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 


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 108
16 January 2019
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
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% 
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric subjects. Please follow the Gilead convention of grading 
any result within the LLN and ULN a 0.


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 109
16 January 2019
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 
>ULN to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
>ULN to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
Adult and Pediatric
1 Year
3.0 to <LLN mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to <LLN mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Infant <1 Year 
3.0 to 3.4 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mEq/L
2.5 to <3.0 mmolL
2.0 to 2.5 mEq/L
2.0 t o <2.5 mmolL
2.0 mEq/L
<2.0 mmolL
Hyperkalemia 
Adult and Pediatric
1 Year
5.6 to 6.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mEq/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Infant <1 Year
>ULN to 6.0 mEq/L
>ULN to 6.0 mmol/L
> 6.0 to 6.5 mEq/L
> 6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
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
Hypocalcemia 
(corrected for albumin if 
appropriate*)
Adult and Pediatric
2 Years
7.8 <LLN mg/dL
1.94 to <LLN mmol/L
7.0 to 7.8 mg/dL
1.74 to 1.94 mmol/L
6.1 to 7.0 mg/dL
1.51 to 1.74 mmol/L
6.1 mg/dL
1.51 mmol/L


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 110
16 January 2019
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Pediatric ≥7 days -2 Years
7.8 to 8.4 mg/dL
1.94 to 2.10 mmol/L
7.0 to <7.8 mg/dL
1.74 to <1.94 mmolL
6.1 to <7.0 mg/dL
1.51 to < 1.74 mmolL
< 6.1 mg/dL
< 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
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
0.63 to LLN mmol/L
1.5 to 2.0 mg/dL
0.47 to 0.63 mmol/L
1.0 to 1.5 mg/dL
0.31 to 0.47 mmol/L
1.0 mg/dL
0.31 mmol/L
Pediatric 1 Year–14 Years 
3.0 to <LLN mg/dL
0.96 to <LLN 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 <LLN mg/dL
1.12 to <LLN 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


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 111
16 January 2019
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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
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
Adult and Pediatric
≥ 1 year
Infant < 1 Year
1.5 mg/dL to LLN
87 μmol/L to LLN
1.0 to 1.5 mg/dL
57 to 87 μmol/L
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
N/A
1.0 mg/dl to <LLN-
57 μmol to <LLN
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
Creatinine** 
1.50 to 2.00 mg/dL
133 to 177 μmol/L
2.00 to 3.00 mg/dL
177 to 265 μmol/L
3.00 to 6.00 mg/dL 
265 to 530 μmol/L
6.00 mg/dL
530 μmol/L
Bicarbonate
Adult and Pediatric 
≥ 4 Years
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
Pediatric < 4 Years
NA
11.0 mEq/Lto <LLN
8.0 to 11.0 mEq/L
8.0 mEq/L
11.0 mmol/L to <LLN
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
NA
500 to 750 mg/dL
5.64–8.47 mmol/L
750 to 1200 mg/dL
8.47–13.55 mmol/L
1200 mg/dL
13.55 mmol/L


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 112
16 January 2019
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
LDL (Fasting)
Adult
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
LDL (Fasting)
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
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
**
An overlap between the Grade 1 scale and the Lab’s normal range for creatinine may result for Male subjects >70 yrs. Please follow the Gilead convention of grading any 
result within the LLN and ULN a 0.


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 113
16 January 2019
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
Pediatrics <16 years 
≥ 16 years
-
2.0 to LLN g/dL
20 to LLN g/L
2.0 g/dL
20 g/L
NA
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


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 114
16 January 2019
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.


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 115
16 January 2019
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
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 


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 116
16 January 2019
CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
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


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 117
16 January 2019
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)


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 118
16 January 2019
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


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 119
16 January 2019
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


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 120
16 January 2019
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)


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 121
16 January 2019
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 
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


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 122
16 January 2019
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
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
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)


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Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 123
16 January 2019
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
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


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 124
16 January 2019
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


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 125
16 January 2019
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]


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 126
16 January 2019
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


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 127
16 January 2019
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


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 128
16 January 2019
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.


GS-9620
Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 129
16 January 2019
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Pregnancy and Contraception Requirements for Males and Females of Childbearing 
Potential
The risks of treatment with GS-9620 during pregnancy have not been evaluated in humans.
Please refer to the latest version of the investigator’s brochure for GS-9620 for the treatment of 
chronic hepatitis B virus and HIV-1 infection for additional information. 
2) Definition of Female of Childbearing Potential
For the purposes of this study, a female subject of childbearing potential is a nonmenopausal
female who has not had a hysterectomy, bilateral oophorectomy, or medically documented
ovarian failure. This definition includes a pubertal female who has not yet started menstruating. 
A woman who has had a tubal sterilization is considered to be of childbearing potential.
A female subject may be considered menopausal in either of the following conditions:

Surgical menopause: Appropriate medical documentation of prior complete bilateral
oophorectomy (ie, surgical removal of the ovaries and occurring at the age at which the
procedure was performed)

Spontaneous menopause: Permanent cessation of previously occurring menses as a result of 
ovarian failure with documentation of hormonal deficiency by a certified health care
provider. The worldwide mean age of spontaneous menopause is 49.24 (SD 1.73) years

A hormonal deficiency should be properly documented in the case of suspected spontaneous 
menopause as follows:
If age ≥54 years and with the absence of normal menses: serum follicle stimulating
hormone (FSH) level elevated to within the postmenopausal range based on the
laboratory reference range where the hormonal assay is performed
If age <54 years and with the absence of normal menses: negative serum or urine 
human chorionic gonadotropin (hCG) with concurrently elevated serum FSH level in the
postmenopausal range, depressed estradiol (E2) level in the postmenopausal range, and
absent serum progesterone level, based on the laboratory reference ranges where the
hormonal assays are performed
3) Contraceptive Requirements
Male subjects and female subjects of childbearing potential who engage in heterosexual
intercourse must agree to utilize protocol specified methods of contraception from the 
screening/enrollment visit throughout the study period and for 36 days following the last dose of 
study drug. Female study subjects who are not heterosexually active must provide periodic 
confirmation of continued abstinence from heterosexual intercourse and regular pregnancy 
testing while taking GS-9620 or placebo. The investigator will counsel subjects on the protocol
specified method(s) for avoiding pregnancy in case the subject chooses to engage in heterosexual 
intercourse.


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Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 130
16 January 2019
Protocol specified contraceptive methods are as follows: (1) a combination of one hormonal
method and one barrier method; or (2) use of an intrauterine device (IUD) or tubal sterilization; 
see Appendix Table 1. Acceptable hormonal methods include injectable progesterone, 
progesterone implants, combination oral contraceptives, transdermal contraceptive patch, and 
vaginal ring. An acceptable barrier method is the male condom. Female subjects must use a 
hormonal method if the partner has a vasectomy. If a subject has undergone tubal sterilization or
has had a Copper T 380A IUD or LNg 20 IUD inserted, no other contraception is needed.
If tubal sterilization is via the Essure procedure, verification of tubal blockage by
hysterosalpingogram (HSP) must be performed approximately 3 months after microinsertion.
Prior to verification, Essure is not considered a reliable form of contraception and the
contraception methods described below must be used. Female subjects who utilize hormonal
contraceptives as one of their birth control methods must have used the same method for at least 
3 months before study dosing.
Female subjects of childbearing potential must have a negative serum pregnancy test at screening 
and a negative urine pregnancy test at baseline (Day 1) prior to receiving the first dose of study 
drug. Lactating females must discontinue nursing before IMP administration.
Appendix Table 1.
Protocol Specified Contraceptive Methods
Single Methods
Combination Methods
Intrauterine Devices (IUDs)

Copper T 380A IUD

LNg 20 IUD
Tubal Sterilization
Estrogen and Progesterone plus Barrier

Combined oral contraceptives plus condom*

Transdermal patch plus condom*

Vaginal ring plus condom*

Implant plus condom*

Injection plus condom*
Partner’s vasectomy must be used with a hormonal method.
*
(without spermicide and excluding lambskin)
The investigator will counsel all subjects on the most effective method(s) for avoiding pregnancy 
during the study. 
4) Additional Requirements for Male Subjects and Recommendations for Partners of 
Female Subjects
Male subjects must agree to use condoms (without spermicide and excluding lambskin) during 
heterosexual intercourse and avoid sperm donation while enrolled in the study and for at least 
90 days after administration of the last dose of study drug. Partners of female subjects should be 
encouraged to use condoms during heterosexual intercourse while enrolled in the study.
Use of condoms, with or without spermicide, has been proven to decrease the risk of
transmission of HIV and other sexually transmitted diseases. The use of spermicide is not
recommended if the subject or subject’s partner is infected with HIV.


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Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 131
16 January 2019
5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days or 4 weeks of last study drug dose. Subjects 
who become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator and discontinue study drug immediately. Subjects whose partner 
has become pregnant or suspects she is pregnant during the study must report the information to 
the investigator. Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome 
are outlined in Section 7.7.2.1.


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Protocol GS–US-382-1450
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 132
16 January 2019
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV
(CDC Guidelines)

Candidiasis of bronchi, trachea, or lungs

Candidiasis of esophagus

Cervical cancer, invasive

Coccidioidomycosis, disseminated or extrapulmonary

Cryptococcosis, extrapulmonary

Cryptosporidiosis, chronic intestinal (1 month duration)

Cytomegalovirus disease (other than liver, spleen or nodes)

Cytomegalovirus retinitis (with loss of vision)

Encephalopathy, HIV-related

Herpes simplex: chronic ulcer(s) (1 month duration); or bronchitis, pneumonitis or 
esophagitis

Histoplasmosis, disseminated or extrapulmonary

Isosporiasis, chronic intestinal (1 month duration)

Kaposi’s sarcoma

Lymphoma, Burkitt’s (or equivalent term)

Lymphoma, immunoblastic (or equivalent term)

Lymphoma, primary, of brain

Mycobacterium avium complex or Myobacterium kansasii, disseminated or extrapulmonary

Mycobacterium tuberculosis, of any site, pulmonary, disseminated or extrapulmonary

Mycobacterium, other species or unidentified species, disseminated or extrapulmonary

Pneumocystis jirovecii (previously known as “Pneumocystis carinii) pneumonia

Pneumonia, recurrent

Progressive multifocal leukoencephalopathy

Salmonella septicemia, recurrent

Toxoplasmosis of brain

Wasting syndrome attributed to HIV infection
CDC Stage-3-Defining Opportunistic Illnesses in HIV Infection - 2014 {Schneider 2008}

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 1b, Randomized, Blinded, Placebo-Controlled 
Dose-Escalation Study of the Safety and Biological Activity of 
GS-9620 in HIV-1 Infected, Virologically Suppressed Adults
Name of Test Drug:
VES (GS-9620)
Study Number:
GS-US-382-1450
Protocol Version (Date):
Amendment 7: 16 January 2019
Analysis Type:
Final Analysis
Analysis Plan Version:
1.0
Analysis Plan Date:
15 May 2019
Analysis Plan Author:
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(rJ GILEAU 


VES (GS-9620)
GS-US-382-1450
Statistical Analysis Plan (Final Analysis) 
Version 1.0
CONFIDENTIAL
Page 2
15 May 2019
TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
PHARMACOKINETIC ABBREVIATIONS................................................................................................................6
1.
INTRODUCTION ................................................................................................................................................7
1.1.
Study Objectives ......................................................................................................................................7
1.2.
Study Design............................................................................................................................................8
1.3.
Sample Size and Power..........................................................................................................................10
2.
TYPE OF PLANNED ANALYSIS ....................................................................................................................11
2.1.
Interim Analyses ....................................................................................................................................11
2.1.1.
Interim Blinded Analyses.....................................................................................................11
2.1.2.
Interim Unblinded Analyses.................................................................................................11
2.2.
Final Analysis ........................................................................................................................................11
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................12
3.1.
Analysis Sets..........................................................................................................................................12
3.1.1.
All Randomized Analysis Set...............................................................................................12
3.1.2.
Full Analysis set...................................................................................................................12
3.1.3.
Safety Analysis Set...............................................................................................................12
3.1.4.
VES Pharmacokinetic Analysis Set......................................................................................13
3.2.
Subject Grouping ...................................................................................................................................13
3.3.
Strata and Covariates..............................................................................................................................13
3.4.
Examination of Subject Subgroups........................................................................................................13
3.5.
Multiple Comparisons............................................................................................................................13
3.6.
Missing Data and Outliers......................................................................................................................14
3.6.1.
Missing Data ........................................................................................................................14
3.6.2.
Outliers.................................................................................................................................14
3.7.
Data Handling Conventions and Transformations .................................................................................14
3.8.
Analysis Visit Windows.........................................................................................................................15
3.8.1.
Definition of Study Day .......................................................................................................15
3.8.2.
Analysis Visit Windows.......................................................................................................16
3.8.3.
Selection of Data in the Event of Multiple Records in a Window .......................................16
4.
SUBJECT DISPOSITION ..................................................................................................................................17
4.1.
Subject Enrollment and Disposition.......................................................................................................17
4.1.1.
Subject Enrollment...............................................................................................................17
4.1.2.
Subject Disposition ..............................................................................................................17
4.2.
Extent of Exposure.................................................................................................................................17
4.3.
Protocol Deviations................................................................................................................................17
5.
BASELINE CHARACTERISTICS....................................................................................................................18
5.1.
Demographics and Baseline Characteristics ..........................................................................................18
5.2.
Baseline Disease Characteristics............................................................................................................18
5.3.
Medical History......................................................................................................................................18
6.
EFFICACY ANALYSES ...................................................................................................................................19
6.1.
Primary Efficacy Analysis .....................................................................................................................19
6.1.1.
Definition of Primary Efficacy Endpoint .............................................................................19
6.1.2.
Statistical Hypotheses for Primary Efficacy Endpoint .........................................................19
6.1.3.
Analysis of Primary Efficacy Endpoint................................................................................19
6.2.
Secondary Efficacy Analyses.................................................................................................................19
6.2.1.
Definition of Secondary Efficacy Endpoints........................................................................19


VES (GS-9620)
GS-US-382-1450
Statistical Analysis Plan (Final Analysis) 
Version 1.0
CONFIDENTIAL
Page 3
15 May 2019
6.2.2.
Analysis of Secondary Efficacy Endpoints ..........................................................................20
6.3.
Other Efficacy Analyses.........................................................................................................................20
6.3.1.
Definition of the Other Efficacy Endpoints..........................................................................20
6.3.2.
Analysis of Other Efficacy Endpoints..................................................................................20
7.
SAFETY ANALYSES........................................................................................................................................22
7.1.
Adverse Events and Deaths....................................................................................................................22
7.1.1.
Adverse Event Dictionary ....................................................................................................22
7.1.2.
Adverse Event Severity........................................................................................................22
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................22
7.1.4.
Relationship of Adverse Events to Study Procedure............................................................22
7.1.5.
Serious Adverse Events........................................................................................................22
7.1.6.
Treatment-Emergent Adverse Events...................................................................................23
7.1.6.1.
Definition of Treatment-Emergent Adverse Events .......................................23
7.1.6.2.
Incomplete Dates ............................................................................................23
7.1.7.
Summaries of Adverse Events and Deaths...........................................................................23
7.1.8.
Additional Analysis of Adverse Events ...............................................................................24
7.2.
Laboratory Evaluations ..........................................................................................................................24
7.2.1.
Summaries of Numeric Laboratory Results .........................................................................25
7.2.2.
Graded Laboratory Values ...................................................................................................25
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities.............................................25
7.2.2.2.
Summaries of Laboratory Abnormalities........................................................25
7.3.
Body Weight, Height, BMI and Vital Signs...........................................................................................26
7.4.
Prior and Concomitant Medications.......................................................................................................26
7.4.1.
Antiretroviral Medications ...................................................................................................27
7.4.2.
Prior Antiretroviral Medications ..........................................................................................27
7.4.3.
Concomitant Non-Antiretroviral Medications......................................................................27
7.5.
Electrocardiogram Results .....................................................................................................................27
7.6.
Other Safety Measures ...........................................................................................................................28
7.7.
Changes From Protocol-Specified Safety Analyses...............................................................................28
8.
PHARMACOKINETIC ANALYSES ................................................................................................................29
8.1.
PK Sample Collection............................................................................................................................29
8.2.
PK Analyses Related to Intensive PK Sampling....................................................................................29
8.2.1.
Estimation of Pharmacokinetic Parameters..........................................................................29
8.2.2.
PK Parameters......................................................................................................................30
8.3.
Statistical Analysis Methods ..................................................................................................................30
8.3.1.
General Considerations for Statistical Analyses ..................................................................30
8.3.2.
Dose Proportionality ............................................................................................................30
9.
REFERENCES ...................................................................................................................................................33
10.
SOFTWARE.......................................................................................................................................................34
11.
SAP REVISION..................................................................................................................................................35
12.
APPENDICES ....................................................................................................................................................36
Appendix 1.
PK Parameters ........................................................................................................................36
Appendix 2.
Schedule of Assessments........................................................................................................37
Appendix 3.
Programming Specification....................................................................................................48
LIST OF IN-TEXT TABLES
Table 8-1.
PK Parameters for VES..........................................................................................................30


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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
ANOVA
analysis of variance
ART
antiretroviral therapy
ARV
antiretroviral
AST
aspartate aminotransferase
BL
baseline
BLQ
below the limit of quantification
BMI
body mass index
CAVR/CAVD
cell-associated HIV-1 RNA/DNA
CRF
case report form
CSR
clinical study report
DLTs
dose-limiting toxicities
DMC
data monitoring committee
ECG
electrocardiogram
ESDD
early study drug discontinuation
eCRF
electronic case report form 
FU
follow-up
GLSM
geometric least-squares means 
GSI
Gilead Sciences, Inc
HLT
high level term
HLGT
high level group term
ICS
intracellular cytokine staining 
ISGs
interferon-stimulated genes 
IVRS
interactive voice response system
IWRS
interactive web response system
LLOQ
lower limit of quantitation
LLT
lower level term
LOQ
limit of quantitation
MAD
multiple ascending dose
MedDRA
medical dictionary for regulatory activities
PBMC
peripheral blood mononuclear cell
PT
preferred term
PVE
Pharmacovigilance and Epidemiology
Q1
first quartile


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Q3
third quartile
SAE
serious adverse event
SAP
statistical analysis plan
SCA
single copy assay
SD
standard deviation
SEC
safety evaluation committee 
SOC
system organ class
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
Upper limit of normal
ULOQ
upper limit of quantification
VES (GS-
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Vesatolimod
WHO
World Health Organization


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PHARMACOKINETIC ABBREVIATIONS
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUCinf
area under the concentration versus time curve extrapolated to infinite time, calculated as AUC0-last
(Clast/z)
%AUCexp
Percentage of AUC extrapolated between AUC0-last and AUCinf
Clast
last observed quantifiable concentration of the drug in plasma
Cmax
maximum observed concentration of drug in plasma
CL/F
apparent oral clearance after administration of the drug:
at single dose: CL/F = Dose/AUCinf , where “Dose” is the dose of the drug
at steady state: CL/F = Dose/AUCtau, where “Dose” is the dose of the drug
T1/2
estimate of the terminal elimination half-life of the drug in plasma, calculated by dividing the 
natural log of 2 by the terminal elimination rate constant (z)
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
Vz/F
apparent volume of distribution of the drug
z
terminal elimination rate constant, estimated by linear regression of the terminal elimination phase 
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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study report (CSR) 
for Study GS-US-382-1450. This SAP is based on the study protocol Amendment 7 dated 
16 January 2019 and the electronic case report form (eCRF). The SAP will be finalized before 
database finalization for the final analysis. Any changes made after the finalization of the SAP 
will be documented in the CSR.
1.1.
Study Objectives
The primary objectives of this study are as follows:

To evaluate the safety and tolerability of escalating, multiple doses of Vesatolimod (VES 
[GS-9620]) in HIV-1 infected virologically suppressed adults on antiretroviral therapy (ART)

To evaluate the virologic effect of VES as measured by changes in plasma HIV-1 RNA
The secondary objectives of this study are as follows:

To evaluate the plasma pharmacokinetics (PK) of VES

To evaluate the pharmacodynamics (PD) of VES as measured by changes in 
interferon-stimulated genes (ISGs) and serum cytokines in whole blood compared to placebo

To evaluate effects of VES on whole blood immune cell activation (CD4 and CD8 T cell, 
NK cell)
The exploratory objectives of this study are as follows:
 
 
 
 
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1.2.
Study Design
This is a phase 1b, randomized, double-blinded, placebo-controlled, multi-cohort dose-escalation 
study with dose cohorts: Cohort 1 (1 mg Dose), Cohort 2 (2 mg Dose), Cohort 3 (4 mg Dose), 
Cohort 4 (6 mg Dose), Cohort 5 (8 mg Dose), Cohort 6 (three administrations of 10 mg Dose, 
followed by seven administrations of 12 mg Dose; Safety Evaluation Committee [SEC] review 
of the 10mg safety data will be required prior to dose escalating to 12mg), and optional Cohort 7
 
 
Two additional optional adaptive cohorts, Cohort 8
 
 and Cohort 9 
 
HIV-1 infected male and non-pregnant, non-lactating female adults who have been virologically 
suppressed (HIV-1 RNA < 50 copies/mL) on ART for ≥12 consecutive months prior to 
screening may be eligible for entry (refer to the protocol for complete inclusion and exclusion 
criteria). Eligible subjects are randomly assigned to 1 of the following 2 treatment groups in a 
6:2 ratio for each cohort. 
.

Cohort 1 (n = 8): Blinded VES 1 mg (n = 6) vs. Placebo (n = 2)

Cohort 2 (n = 8): Blinded VES 2 mg (n = 6) vs. Placebo (n = 2)

Cohort 3 (n = 8): Blinded VES 4 mg (n = 6) vs. Placebo (n = 2)

Cohort 4 (n = 8): Blinded VES 6 mg (n = 6) vs. Placebo (n = 2)

Cohort 5 (n = 8): Blinded VES 8 mg (n = 6) vs. Placebo (n = 2)

Cohort 6 (n = 8): Blinded VES 10/12 mg (n = 6) vs. Placebo (n = 2)
Central randomization is used. Enrollment will initially be opened for Cohort 1 only. The SEC 
will review study progress, safety and virology results of enrolled subjects. After all subjects in a 
cohort have received at least three doses (Cohorts 1 to 3, and 6) or five doses (Cohorts 4 and 5), 
the SEC will review safety data from that cohort, including adverse events (AEs) and clinical 
laboratory results (including plasma HIV-1 RNA) before approving the next dose escalation. 
A cohort may be suspended if ≥2 out of 6 subjects 
receiving VES experience one or more dose-limiting toxicities (DLTs) considered related to 
study drug. Subjects will receive a total of either 6 doses in Cohorts 1 to 3, 10 doses in Cohorts 4 
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to 6, 
 of their assigned study treatment administered 
once every other week. For all subjects in Cohort 6, Dose 4 (Day 43) will occur after SEC review 
has been completed. If dose escalation is approved by the SEC, subjects in Cohort 6 will receive 
12 mg of VES or placebo from Doses 4 to 10; if dose escalation is not approved by the SEC, 
subjects will continue receiving 10 mg of VES or placebo from Doses 4 to 10.
For Cohorts 1 to 3, dosing visits will occur at Day 1, Day 15, Day 29, Day 43, Day 57, and 
Day 71. For Cohorts 4 to 9, dosing visits will occur at Day 1, Day 15, Day 29, Day 43, Day 57, 
Day 71, Day 85, Day 99, Day 113 and Day 127. 
 
 For Cohorts 1 to 4, subjects will fast for at least 
2 hours before dosing. For Cohorts 5 to 8, subjects will fast overnight (at least 8 hours) before 
dosing. 
 
 The Investigator will verify the subject’s continued eligibility for dosing at post-Baseline 
dosing visits, including the absence of DLTs and (for females of childbearing potential) a 
negative urine pregnancy test, prior to dosing. All doses will be directly administered by blinded 
site staff.
Laboratory analyses (hematology, serum chemistry, and urinalysis) will be performed weekly for 
Cohorts 1 to 3. For Cohorts 4 to 9, these labs will be collected on dosing days, seven days post 
dose (starting from Dose 4), at end of study, and early study drug discontinuation (ESDD). For 
Cohorts 6 
 these labs will also be collected on Day 2 and two days post dose (starting from 
Dose 5).
 
Urine pregnancy test (for females of childbearing potential) will 
be performed prior to each dose. Vital signs (blood pressure, pulse, respiration rate and 
temperature) will be measured at all dosing visits.
Plasma HIV-1 RNA will be measured at every visit except Pre-Baseline (Day -13). Cell-
associated HIV-1 RNA/DNA (CAVR/CAVD), and plasma HIV-1 RNA by SCA will be 
collected immediately before and two days post Doses 1, 4, 6 and at end of the study (Cohort 1 
to 3); immediately before and two days post Doses 1, 5, 10 and at end of the study (Cohorts 4 to
9).
 
 
Peripheral blood immune cell numbers for T/B/NK/pDC/mDC including: CD4 and CD8 
populations, CD4/CD8 ratio, CD4% and lymphocyte activation (T, B and NK cells) by flow 
cytometry will be collected immediately before and two days post Doses 1, 3, and 6 (Cohorts 1 
to 3), and immediately before and two days post Doses 1, 5, 10 and at end of the study 
(Cohorts 4 to 9). FoxP3+ Treg cells by flow cytometry will be collected immediately before 
Doses 1, 3, and 6 (Cohorts 1 to 3), and immediately before Doses 1, 5 and 10 (Cohort 4 to 9). 
 
 
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Changes in the levels of antiviral cytokines and inflammatory markers by chemiluminescence
will be collected immediately before and 2 days and 7 days after each dose, and at the end of the 
study (Cohorts 1 to 3). For subjects in Cohorts 4 to 9, they will be collected immediately before, 
post dose days 1, 2 and 7 after Doses 1, 4 (only if Cohort 6 subjects receive 12 mg at Dose 4), 5 
and 10. 
 
PBMC intracellular cytokine staining (ICS) for Treg cells will be done immediately before and 
2 days after Doses 1 and 6 for subjects in Cohorts 1 to 3. HIV-specific T-cell responses by 
ELISPOT will be collected at Pre-Baseline/Day -13, immediately before Dose 6 and at the end of 
study for subjects in Cohorts 1 to 3. For subjects in Cohorts 4 to 9, HIV-specific polyfunctional 
T cell ICS and HIV-specific T-cell responses by ELISPOT will be collected at 
Pre-Baseline/Day -13 and at the end of the study. 
 
Whole blood ISG mRNA panel will be performed immediately before and 2 days and 7 days 
after each dose of study drug and at the end of the study (Day 101) (for Cohorts 1 to 3) and 
immediately before and 1, 2 and 7 days after Doses 1, 4 (only if Cohort 6 subjects receive 12 mg 
starting at Dose 4), 5 and 10.
 
Assessments of adverse events, concomitant medications and symptom-directed physical 
examination are performed at each visit.
Blood samples will be collected to determine plasma VES concentrations and plasma ARV 
concentrations at the following time points relative to study drug dosing:
Plasma VES concentrations at the following time points for all cohorts:

Pre-dose (≤5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 12 hours post dose at Day 1; 
then one sample 48 hours post dose at Day 3

If the SEC approves the dose escalation to 12 mg in Cohort 6, starting from Dose 4 and 
onwards, plasma VES concentrations will also be collected on Day 43 (Dose 4): Pre-dose 
(≤5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 12 hours post dose; then one sample 
48 hours post dose at Day 45.
Plasma ARV concentrations: a single trough ARV PK sample will be collected at 
Pre-Baseline/Day -13 (Cohorts 1 to 3) or at Screening, Day 29, Day 57, Day 85 and Day 99 
(Cohort 5), or at Screening, Day 57 and Day 99 (Cohorts 6
 
1.3.
Sample Size and Power
No power calculation was performed because this is an exploratory study to characterize the 
safety and efficacy of VES in HIV-1 infected patients.
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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
2.1.1.
Interim Blinded Analyses
SEC will review the progress of the study and perform interim reviews of the safety data in order 
to protect subject welfare and preserve study integrity. To ensure the best interests of the 
participants, the SEC will recommend to the sponsor if the nature, frequency, and severity of 
adverse effects associated with the study treatment warrant the early termination of the study, the 
continuation of the study, or the continuation of the study with modifications.
The initial meeting of the SEC has occurred prior to the first dose of Cohort 1. This meeting 
formally established the SEC and thoroughly acquainted the SEC with the protocol and the SEC 
Charter. Subsequent SEC analyses have been performed after all subjects enrolled in each Cohort 
received at least three doses (Cohorts 1 to 3, and 6) or five doses (Cohorts 4 to 5) to review the 
safety and virology data before approving the opening of enrollment in the next Cohort or dose 
escalation within the same Cohort (Cohort 6).
The SEC’s role and responsibilities and the scope of analysis to be provided to the SEC are 
provided in a mutually agreed upon charter, which defines the SEC membership, meeting 
logistics, and meeting frequency.
2.1.2.
Interim Unblinded Analyses
Prior to the final analysis, selected individuals from Gilead were unblinded to assess the interim 
safety, virology, biomarker, and PK data of VES. This group may consist of at least one 
representative from Clinical Research, Biostatistics, Clinical Pharmacology, 
Pharmacovigilance/Epidemiology, Biomarkers, Clinical Virology and may include other 
personnel as necessary.
The access to individual unblinded data (safety, virology, biomarker and PK) was limited only to 
data relevant for analysis by the function representatives and was summarized at the group level 
for regulatory documents and external submissions without revealing individual subject 
identification to protect study blind at the subject level. This group reviewed data (safety, 
virology, biomarker and PK) to support development of new clinical protocols, regulatory 
documents, and conference submissions.
2.2.
Final Analysis
After all subjects have completed the study, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized, the study blind will be
broken and the final analysis of the data will be performed.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard error (SE), median, 
first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
All statistical tests will be 2-sided and performed at the 5% significance level unless otherwise 
specified.
By-subject listings will be presented for all subjects in the All Randomized Analysis Set and 
sorted by subject ID number, visit date, and time (if applicable), unless specified otherwise. Data 
collected on log forms, such as AEs, will be presented in chronological order within the subject. 
The treatment group to which subjects were randomized will be used in the listings. Age, sex at 
birth, race, and ethnicity will be included in the listings, as space permits.
3.1.
Analysis Sets
Analysis sets define the subjects to be included in an analysis. Analysis sets and their definitions
are provided in this section. Subjects included in each analysis set will be determined before the 
study blind is broken for analysis. The analysis set will be identified and included as a subtitle of 
each table, figure, and listing. A summary of the number and percentage of subjects in each 
analysis set will be provided by treatment group and in total for all cohorts combined.
3.1.1.
All Randomized Analysis Set
The All Randomized Analysis Set includes all subjects who were randomized into the study.
This is the primary analysis set for by-subject listings.
3.1.2.
Full Analysis set
The Full Analysis Set (FAS) will include all subjects who (1) were randomized into the study 
and (2) have received at least one dose of study drug. Subjects will be grouped according to the 
treatment to which they were randomized. For the FAS, all efficacy data, including data 
collected after the last dose of study drug, will be included, unless specified otherwise. This is 
the primary analysis set for efficacy analyses.
3.1.3.
Safety Analysis Set
The Safety Analysis Set will include all subjects who (1) were randomized into the study and 
(2) have received at least 1 dose of study drug. All the data collected up to 30 days after 
permanent discontinuation of the study drug will be included in the safety summaries, unless 
specified otherwise. Subjects will be grouped according to the treatment they actually received. 
This is the primary analysis set for safety analyses.


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3.1.4.
VES Pharmacokinetic Analysis Set
The VES PK Analysis Set will include all subjects who (1) were randomized into the study, (2) 
have received at least 1 dose of active VES, and (3) have at least 1 nonmissing steady state PK 
parameter for VES. This is the primary analysis set for detailed PK analysis of intensive PK 
sampling.
3.2.
Subject Grouping
For analyses based on the All Randomized Analysis Set or the FAS, subjects will be grouped by 
randomized treatment. For other analyses, subjects will be grouped by actual treatment received. 
The actual treatment received will differ from the randomized treatment only when the actual 
treatment received differs from randomized treatment for the entire treatment duration.
Subjects who received placebo in different cohorts will be combined as one placebo group for 
analysis purposes if applicable. The treatment groups for analysis are defined as follows:

Treatment 1: VES 1 mg (in Cohort 1)

Treatment 2: VES 2 mg (in Cohort 2)

Treatment 3: VES 4 mg (in Cohort 3)

Treatment 4: VES 6 mg (in Cohort 4)

Treatment 5: VES 8 mg (in Cohort 5)

Treatment 6: VES 10/12 mg (in Cohort 6)

Treatment 7: Placebo (in all Cohorts)
3.3.
Strata and Covariates
This study does not use a stratified randomization schedule in enrolling subjects. No covariates 
will be included in analyses.
3.4.
Examination of Subject Subgroups
There are no pre-specified subject subsets for efficacy or safety analyses.
3.5.
Multiple Comparisons
All endpoint tests will be done at the significance level of 0.05 with no multiplicity adjustment in 
this proof-of-concept study.


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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
A missing datum for a given study analysis window may be due to any of the following reasons:

A visit occurring in the window but data were not collected or were unusable 

A visit not occurring in the window

A subject prematurely discontinuing from the study before reaching the window
In general, values for missing data will not be imputed, unless methods for handling missing data 
are specified.
The handling of missing or incomplete dates for AE onset is described in Section 7.1.6.2, and for 
concomitant medications in Section 7.4.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted to evaluate the impact of outliers on efficacy or safety 
outcomes, unless specified otherwise. All data will be included in the data analyses.
3.7.
Data Handling Conventions and Transformations
Laboratory data that are continuous in nature but are less than the lower limit of quantitation
(LLOQ) or above the upper limit of quantitation (ULOQ) will be imputed as follows except for 
urine creatinine:

A value that is 1 unit less than the limit of quantitation (LOQ) will be used to calculate 
descriptive statistics if the datum is reported in the form of “x” (where x is considered the 
LOQ). For example, if the values are reported as < 50 and < 5.0, values of 49 and 4.9, 
respectively, will be used to calculate summary statistics. An exception to this rule is any 
value reported as < 1 or < 0.1, etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, 
respectively, will be used to calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).
For urine creatinine, a value of “< 1” is handled as a missing value in its summary and the 
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Logarithmic (base 10) transformations will be applied to HIV-1 RNA data for efficacy analyses. 
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purposes. 
Biomarker values that are below the limit of quantitation (BLQ) will be presented as “BLQ” in 
the data listing. Values that are BLQ will be treated as LLOQ at both predose and postbaseline 
time points.
Natural logarithm transformation will be used for plasma/blood concentrations and analysis of 
PK parameters. Plasma concentration values that are below BLQ will be presented as “BLQ” in 
the concentration data listing. Values that are BLQ will be treated as 0 at pre-dose time points, 
and one-half the value of the LLOQ at postbaseline time points.
The following conventions will be used for the presentation of summary and order statistics: 

If at least 1 subject has a concentration value of BLQ for the time point, the minimum value 
will be displayed as “BLQ.”

If more than 25% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.”

If more than 50% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.”

If more than 75% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.”

If all subjects have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) will be displayed as “BLQ.”
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the first dosing date of study drug and derived as follows:

For postdose study days: Assessment Date – First Dosing Date + 1

For days prior to the first dose: Assessment Date – First Dosing Date
Therefore, study day 1 is the day of first dose of study drug administration.


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3.8.2.
Analysis Visit Windows
The nominal visit as recorded on the CRF or lab date will be used when data are summarized by 
visit. Any data relating to unscheduled visits will not be assigned to a particular visit or time 
point and will not be included in the summary tables, but will be included in the listings. 
However, the following exceptions will be made:

An unscheduled visit prior to the first dosing of study drug may be included in the calculation 
of the baseline value, if applicable.

Unscheduled visits after the first dose of study drug will be included in determining the 
maximum postbaseline toxicity grade.

For subjects who prematurely discontinue from the study, early termination (ET) data will be 
summarized as a separate visit, labeled as “Early Termination Visit”.

Data obtained after the follow-up visit or last dose date plus 30 days (whichever is later) will 
be excluded from the summaries, but will be included in the listings.
3.8.3.
Selection of Data in the Event of Multiple Records in a Window
Depending on the statistical analysis method, single values may be required for each day. For 
example, change from baseline by visit usually requires a single value. 
If multiple valid, nonmissing, numeric measurements exist on the same nominal visit, records 
will be chosen based on the following rules if a single value is needed:

In general, the baseline value will be the last nonmissing value on or prior to the first dosing 
date of study drug, unless specified differently. If multiple measurements occur on the same 
day, the last nonmissing value prior to the time of first dosing of study drug will be 
considered as the baseline value. If these multiple measurements occur at the same time or 
the time is not available, the average (arithmetic or geometric mean, as appropriate) of these 
measurements (for continuous data) will be considered the baseline value.

For postbaseline values:
If there is more than one record on the selected day, the average will be taken (geometric 
mean for HIV-1 RNA and arithmetic mean for others), unless otherwise specified.
If multiple valid, nonmissing, categorical measurements exist on the same nominal visit, records 
will be chosen based on the following rule if a single value if needed:

For baseline, the last available record on or prior to the first dose of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, the value with the lowest severity will be selected (eg, normal will be selected over 
abnormal for safety ECG findings).

For postbaseline visits, the value for the scheduled visit only will be used. If multiple records 
are available for a scheduled visit, the most conservative value within that day will be 
selected (eg, abnormal will be selected over normal for safety ECGs).


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
4.1.1.
Subject Enrollment
A summary of subject enrollment will be provided by treatment group for each country, 
investigator within a country and overall for all cohorts combined. The summary will present the 
number and percentage of subjects enrolled. The denominator for the percentage calculation will 
be the total number of enrolled subjects for that column. 
The randomization schedule used for the study will be provided as an appendix to the clinical 
CSR.
4.1.2.
Subject Disposition
The summary of subject disposition will be provided by treatment group and overall for all 
screened subjects for all cohorts combined. This summary will include the number of subjects 
screened, screen failure subjects who were not randomized, subjects who met all eligibility 
criteria and were not randomized, subjects randomized, subjects randomized but never treated, 
subjects in the safety analysis set, and subjects in the FAS.
In addition, the number and percentage of the subjects in the following categories will be 
summarized:
1) Completed study drug
2) Prematurely discontinuing study drug (with summary of reasons for discontinuing study 
drug)
3) Completed the study
4) Prematurely discontinuing from study (with summary of reasons for discontinuing study).
The denominator for the percentages of subjects in each category will be the number of subjects 
in the safety analysis set. 
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation will be provided.
4.2.
Extent of Exposure
A subject’s extent of exposure to study drug data will be generated from the study drug 
administration page in the eCRF. Exposure data will be listed.
4.3.
Protocol Deviations 
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. The number and percentage of subjects with important protocol deviations by 
deviation reason and the total number of important protocol deviations by deviation reason 
(eg, nonadherence to study drug, violation of select inclusion/exclusion criteria) will be 
summarized by treatment group for the Full Analysis Set. A by-subject listing will be provided 
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5.
BASELINE CHARACTERISTICS 
5.1.
Demographics and Baseline Characteristics
Subject demographic data (eg, age, sex at birth, race, and ethnicity) and baseline characteristics 
(eg, body weight, height, and body mass index [BMI]) will be summarized by treatment group 
and overall for all cohorts combined using descriptive statistics (n, mean, SD, median, Q1, Q3, 
minimum, and maximum) for continuous data and by the number and percentage of subjects for 
categorical data. The summaries of demographic data and baseline subject characteristics will be 
provided for the safety analysis set.
5.2.
Baseline Disease Characteristics
The following baseline disease characteristics will be summarized:

HIV-1 RNA (log10 copies/mL)

HIV-1 RNA categories (copies/mL) (a) < 50 and (b) ≥ 50 

CD4 cell count (/μL)

CD4+ cell count categories (/μL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥ 200 to < 350, (d) ≥350 to 
< 500, and (e) ≥500

CD4 percentage (%)

eGFRCG (mL/min)

Mode of infection (HIV risk factors)

HIV disease status

Duration of being diagnosed with HIV disease (in years)

Duration of ARV prior to study (in years)

Pre-ARV HIV-RNA viral set point (log10 copies/mL)

Pre-ARV HIV-RNA categories (copies/mL): (a) ≤ 100,000, (b) 100,000 to ≤ 400,000 , and 
(c) 400,000

Pre-ARV CD4 cell count (/μL)

Pre-ARV CD4 cell count categories (/μL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥200 to < 350, 
(d) ≥ 350 to < 500, and (e) ≥500
5.3.
Medical History
General medical history data will be collected at screening and listed only. General medical 
history data will be coded using the current version of Medical Dictionary for Regulatory 
Activities (MedDRA).


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6.
EFFICACY ANALYSES
As this study is still in phase I of the drug development, p-values from statistical comparisons 
will not be adjusted for multiplicity, so the results should be interpreted with caution. 
6.1.
Primary Efficacy Analysis
6.1.1.
Definition of Primary Efficacy Endpoint
The primary efficacy endpoint is the maximum change from baseline in plasma log10
HIV-1 RNA at any postdose timepoint up to Day 81 for Cohorts 1-3 or Day 134 for Cohorts 4-6.
6.1.2.
Statistical Hypotheses for Primary Efficacy Endpoint
The analysis of maximum change from baseline in plasma log10 HIV-1 RNA at any postdose 
timepoint up to Day 81 for Cohorts 1-3 or Day 134 for Cohorts 4-6 between a VES treatment 
group and pooled placebo group is exploratory in nature and no formal hypothesis testing was 
planned. 
6.1.3.
Analysis of Primary Efficacy Endpoint
The maximum change from baseline in plasma log10 HIV-1 RNA at any postdose timepoint up to 
Day 81 for Cohorts 1-3 or Day 134 for Cohorts 4-6 will be calculated for all subjects in the full
analysis set using available on-treatment HIV-1 RNA data up to Day 81 for Cohorts 1-3 or Day 
134 for Cohorts 4-6, and summarized by treatment group using descriptive statistics (n, mean, 
SD, 95% CI, median, Q1, Q3, minimum, and maximum).
The primary efficacy endpoint will be compared between each active treatment group and the 
pooled placebo group using a Wilcoxon rank sum test at a two-sided 0.05 significant level. 
6.2.
Secondary Efficacy Analyses
6.2.1.
Definition of Secondary Efficacy Endpoints
Secondary efficacy endpoints include the following: 

Change from baseline in plasma log10 HIV-1 RNA at postbaseline visits

Proportion of subjects with plasma HIV-1 RNA ≥50 copies/mL at any postdose timepoint 
(up to 10 days after each dose for Cohorts 1-3 and 7 days after each dose for Cohorts 4-6)


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6.2.2.
Analysis of Secondary Efficacy Endpoints
The full analysis set will be used for secondary efficacy endpoint analysis. 
Baseline and change from baseline in plasma log10 HIV-1 RNA at postbaseline visits will be 
summarized by treatment group using descriptive statistics. The change from baseline in plasma 
log10 HIV-1 RNA at postbaseline visits will be analyzed in the same fashion as that of the 
primary efficacy endpoint.
The number and proportion of subjects with plasma HIV-1 RNA ≥50 copies/mL at any postdose 
timepoint (up to 10 days after each dose for Cohorts 1-3 and 7 days after each dose for Cohorts 
4-6) will be summarized by treatment group and compared between each active treatment group 
and the pooled placebo group using a Fisher’s exact test at a two-sided 0.05 significant level. The 
number and percentage of subjects with HIV-1 RNA in the following categories will be 
summarized:

≥ 50 copies/mL

< 50 copies/mL
6.3.
Other Efficacy Analyses
6.3.1.
Definition of the Other Efficacy Endpoints
Other efficacy endpoints include the following:

Change, percentage change and fold change from baseline in the levels of serum cytokines 
(including IFN-, IL-1RA, IP-10, and ITAC)

Fold change in mRNA for ISGs including MX1, OAS1 and ISG15

Change and percentage change from baseline in CD4/CD38/HLADR, CD8/CD38/HLADR 
and NK cell activation
6.3.2.
Analysis of Other Efficacy Endpoints
The full analysis set will be used for other efficacy endpoint analysis. 
Change percentage change and fold change from baseline (postbaseline/baseline) in the levels of 
serum cytokines will be summarized by treatment group using descriptive statistics and 
compared between each active treatment group and the pooled placebo group using a Wilcoxon 
rank sum test at a two-sided 0.05 significant level.
Fold change from baseline (postbaseline/baseline) in mRNA for ISGs will be analyzed similarly 
as above.


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Change and percentage change from baseline in CD4/CD38/HLADR, CD8/CD38/HLADR and 
NK cell activation will also be analyzed similarly as above.


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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of 
MedDRA. System organ class (SOC), high-level group term (HLGT), high-level term (HLT), 
preferred term (PT), and lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe), or Grade 4 (life threatening) according to toxicity criteria specified in the protocol. The 
severity grade of events for which the investigator did not record severity will be categorized as 
“missing” for tabular summaries and data listings. The missing category will be listed last in 
summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Study drug related AEs are those for which the investigator selected “Related” on the AE CRF to 
the question of “Related to Study Treatment.” Relatedness will always default to the 
investigator’s choice, not that of the medical monitor. Events for which the investigator did not 
record relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Relationship of Adverse Events to Study Procedure
Study procedure related AEs are those for which the investigator selected “Yes” on the AE CRF 
to the question of “Related to Study Procedures.” Relatedness will always default to the 
investigator’s choice, not that of the medical monitor. Events for which the investigator did not 
record relationships to study procedure will be shown as missing from that captured on the CRF 
in by-subject data listings.
7.1.5.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE that were specified in the study protocol. SAEs captured and stored in the clinical 
database will be reconciled with the SAE database from the Gilead Pharmacovigilance and 
Epidemiology (PVE) Department before database finalization.


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7.1.6.
Treatment-Emergent Adverse Events
7.1.6.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as one or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days 
after permanent discontinuation of study drug

Any AEs leading to premature discontinuation of study drug
7.1.6.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
either of the following 2 criteria is met:

The AE onset and end dates are the same as or after the month and year (or year) of the 
first dosing date of study drug

The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to 30 days after the date of the last dose of study drug
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, will be considered to be treatment emergent.
7.1.7.
Summaries of Adverse Events and Deaths
A brief high-level summary of TEAEs will be provided by treatment for the number and 
percentage of subjects who had the following: any TEAE; any TEAE of Grade 3 or above; any 
serious TEAE; any study drug-related TEAE; any study drug-related serious TEAE; any TEAE 
that led to premature discontinuation of study drug. The treatment-emergent deaths observed 
during the study will also be summarized and included in this table. Treatment-emergent death 
refers to the death occurred between the first dose date and the last dose date plus 30 days, 
inclusive.
Adverse event summaries will provide the number and percentage of subjects with AEs by SOC 
and PT, by treatment based on the Safety Analysis Set as follows:

All AEs

All AEs by severity

AEs of Grade 3 or above

All study-drug related AEs


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
All SAEs

All study-drug related SAEs

All AEs leading to premature discontinuation of study drug
Multiple events will be counted only once per subject per treatment in each summary. An AE 
that starts in one treatment period and continues into the following treatment period(s) will be 
counted only in the period in which the AE began. Adverse events will be summarized and listed 
first in alphabetic order of SOC and then by PT in order of descending incidence of the pooled 
treatment groups within each SOC. For summaries by severity, the most severe grade will be 
used for those AEs that occurred more than once in an individual subject per treatment during the 
study. 
In addition to the by-treatment summaries described above, data listings will be provided for the 
following:

All AEs (with a variable indicating whether the event is treatment emergent)

SAEs

Deaths

AEs leading to premature discontinuation of study drug
7.1.8.
Additional Analysis of Adverse Events
No additional analysis of adverse events is planned.
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to the last dose of study drug plus 30 days. 
The analysis will be based on values reported in conventional units. When values are BLQ, they 
will be listed as such, and the imputed value will be used for the purpose of calculating summary 
statistics. 
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and urinalysis separately. Values falling 
outside of the relevant reference range and/or having a severity grade of 1 or higher on the 
Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be
flagged in the data listings, as appropriate.
No inferential statistics will be generated.


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7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment for each laboratory test specified in the study 
protocol as follows:

Baseline values 

Values at each postbaseline time point

Change from baseline at each postbaseline time point
A baseline laboratory value will be defined as the last measurement obtained on or prior to the 
date/time of first dose of study drug. Change from baseline to a postbaseline visit will be defined 
as the visit value minus the baseline value. The mean, median, Q1, Q3, minimum, and maximum 
values will be displayed to the reported number of digits; SD values will be displayed to the 
reported number of digits plus 1.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.
7.2.2.
Graded Laboratory Values
The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be 
used to assign toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 includes all 
values that do not meet the criteria for an abnormality of at least Grade 1. For laboratory tests 
with criteria for both increased and decreased levels, analyses for each direction (ie, increased, 
decreased) will be presented separately. If there is any lab toxicity grading scale overlapping 
with normal reference ranges (eg, grade 1 scale overlaps with normal reference ranges), 
laboratory values within normal range will not be graded.
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of 
last dose of study drug plus 30 days. If the relevant baseline laboratory value is missing, any 
abnormality of at least Grade 1 observed within the time frame specified above will be 
considered treatment emergent.
7.2.2.2.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
subjects in the study with the given response at baseline and each scheduled postbaseline time 
point.


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The following summary (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment; subjects will be categorized according 
to the most severe postdose abnormality grade for a given lab test within a treatment:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 and 4 laboratory abnormalities

Treatment-emergent Grade 2, 3 and 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
non-missing postbaseline values up to 30 days after last dosing date.
A by-subject listing of treatment-emergent Grade 3 or 4 laboratory abnormalities will be 
provided by subject ID number and visit in chronological order. This listing will include all test 
results that were collected throughout the study for the lab test of interest, with all applicable 
severity grades displayed.
7.3.
Body Weight, Height, BMI and Vital Signs
Descriptive statistics will be provided by treatment group for body weight, BMI and vital signs 
as follows:

Baseline value

Values at each postbaseline visit

Change from baseline at each postbaseline visit
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of vital signs will be provided by subject ID number and visit in 
chronological order. In the same manner, a by-subject listing of body weight, height, and BMI
will be provided separately.
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the Gilead-modified World Health Organization (WHO) Drug dictionary.
All prior and concomitant medications (other than per-protocol study drugs) will be provided in a 
by-subject listing sorted by subject ID number and administration date in chronological order.


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7.4.1.
Antiretroviral Medications
Any ARV medications used prior to, during, or after the study (if collected) are all recorded on 
the ARV eCRF. All ARV medications recorded on the ARV eCRF will be coded using the
Gilead-modified World Health Organization (WHO) Drug Dictionary for ARV medication. The 
WHO preferred name and drug code will be attached to the clinical database. All ARV 
medications recorded on the ARV eCRF will be listed. No inferential statistics will be provided.
7.4.2.
Prior Antiretroviral Medications
Prior ARV medications are defined as ARV medications taken on or up to 2 days prior to the 
first dose date of randomized study drug based on ARVs reported on ARV eCRF.
7.4.3.
Concomitant Non-Antiretroviral Medications
Concomitant non-ARV medications (ie, non-ARV medications other than study drug that are 
taken while receiving study drug) will be coded using the WHO Drug Dictionary. The WHO 
preferred name and drug code will be attached to the clinical database. Use of concomitant 
medications will be summarized (number and percentage of subjects) by treatment group, WHO 
drug class and preferred name. Multiple drug use (by preferred name) will be counted only once 
per subject. The summary will be sorted alphabetically by drug class and then by decreasing total 
frequency within a class.
If the start or stop date of non-ARV medications is incomplete, the month and year (or year 
alone, if month is not recorded) of the start or stop date will be used to determine whether the 
non-ARV medications are concomitant or not. The medication is concomitant if the month and 
year of the start or stop (or year of the start or stop, if month is not recorded) of the medication 
does not meet either of the following criteria:

The month and year of start of the medication is after the last dose date

The month and year of stop of the medication is before the first dose date
If the start and stop date of non-ARV medications are complete, the start date is not after the 
last dose date and the stop date is not before the first dose date, or the non-ARV medications are 
marked as ongoing and start date is on or before the last dose date, the non-ARV medications are 
concomitant for the study.
Summaries of non-ARV concomitant medications will be provided for the safety analysis set. 
Subjects with any non-ARV concomitant medications will be listed. No inferential statistics will 
be provided.
7.5.
Electrocardiogram Results
Electrocardiogram (ECG) data will not be presented in the CSR since ECGs were not assessed in 
this study other than as part of the screening process for potential new subjects.


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7.6.
Other Safety Measures
A by-subject listing of subject pregnancies during the study will be provided by subject ID 
number. No additional safety measures are specified in the protocol.
Although not necessarily related to safety, a by-subject listing of all comments received during 
the study on the comments form will be provided by subject ID number, and form for which the 
comment applies.
7.7.
Changes From Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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8.
PHARMACOKINETIC ANALYSES
8.1.
PK Sample Collection
Plasma VES (concentrations will be collected at the following time points for all cohorts
relative to the Dose 1 on Day 1:

Pre-dose (≤5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 12 hours post-dose at Day 1; 
then one sample 48 hours post dose at Day 3
Plasma VES concentrations will be collected at the following time points for Cohort 6 relative 
to the Dose 4 on Day 43:

Pre-dose (≤5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 12 hours post dose at 
Day 43; then one sample 48 hours post-dose at Day 45.
8.2.
PK Analyses Related to Intensive PK Sampling
VES PK parameters will be determined in subjects in the VES PK analysis set. Concentrations of 
VES in plasma will be determined using validated bioanalytical assays.
8.2.1.
Estimation of Pharmacokinetic Parameters
PK parameters will be estimated using Phoenix WinNonlin® software using standard 
noncompartmental methods. The linear/log trapezoidal rule will be used in conjunction with the 
appropriate noncompartmental model, with input values for dose level, dosing time, plasma 
concentration, and corresponding real-time values, based on drug dosing times whenever 
possible.
All predose sample times before time-zero will be converted to 0. 
For area under the curve (AUC), samples BLQ of the bioanalytical assays occurring prior to the 
achievement of the first quantifiable concentration will be assigned a concentration value of 0 to 
prevent overestimation of the initial AUC. Samples that are BLQ at all other time points will be 
treated as missing data in WinNonlin®. The nominal time point for a key event or dosing interval 
(τ) may be used to permit direct calculation of AUC over specific time intervals. The 
appropriateness of this approach will be assessed by the PK scientist on a profile-by-profile 
basis.
Pharmacokinetic parameters such as AUCinf, λz and t1/2 are dependent on an accurate estimation 
of the terminal elimination phase of drug. The appropriateness of calculating these parameters 
will be evaluated upon inspection of PK data on a profile-by-profile basis by the PK scientist.


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8.2.2.
PK Parameters
Pharmacokinetic parameters will be generated for all subjects for whom parameters can be 
derived. The analyte and parameters will be used to evaluate the PK objectives of the study. The 
primary PK parameters are AUClast, AUCinf, and Cmax of VES.
Table 8-1.
PK Parameters for VES
Analyte
Parameters
VES (Single Dose)
Cmax, Tmax, Clast, Tlast, AUClast, AUCinf, %AUCexp, T1/2, Vz/F, CL/F, and 
8.3.
Statistical Analysis Methods
8.3.1.
General Considerations for Statistical Analyses
Individual subject concentration data and individual subject PK parameters of VES will be listed 
and summarized for subjects in the VES PK analysis set by treatment. Summary statistics 
(n, mean, SD, coefficient of variation [CV(%)], minimum, median, maximum, Q1, Q3) will be 
presented by treatment group. The number of subjects with concentration values BLQ will be 
presented. The geometric mean, geometric mean 95% CI, and the mean and SD of the natural 
log-transformed values will be presented for all PK parameters in addition to the summaries 
mentioned above.
Plasma concentrations over time will be plotted in the semi-logarithmic and linear scale as mean 
± SD, and median (Q1, Q3) by treatment. In addition, individual subject plasma concentrations 
over time will be plotted by treatment group. 
8.3.2.
Dose Proportionality 
If data are available, dose proportionality will be obtained by comparing PK parameters of VES 
across all dose levels for Cohorts 1-6.
Dose proportionality will be evaluated based on the power model and the ANOVA method.
The following PK parameters and dose levels will be included in both the power model and 
ANOVA method:
Day
Doses (mg)
PK Parameters
VES (single dose)
1
1, 2, 4, 6, 8, 10, 12
AUClast, AUCinf, Cmax


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Power Model
The dose proportionality analysis will be addressed in terms of point estimates and CIs of 
statistical model parameters (slopes). The power model has the general equation y = β0 x dose β1
where 
represents the dependent variables, eg, AUClast, AUCinf, and Cmax for VES single-dose. 
The exponent β1 in the model will be assessed by regressing the natural log-transformed PK 
parameter on the natural log-transformed dose{Smith 2000},
log (y) = log (β0) + β1 log (dose)
The population mean slope 
and corresponding 90% confidence interval (CI) will be 
estimated.
The following SASPROC MIXED code will provide the analysis and the 90% CI calculations 
for natural log-transformed Cmax. Similar code will be used for other natural log-transformed 
parameters. 
proc mixed;
  class subjid;
  model lncmax = lndose / ddfm=kr;
  estimate “Slope of log dose” lndose 1/ cl alpha=0.10; 
  make ‘estimates’ out=slope1; 
run;
Due to the exploratory nature of the analysis, no dose proportionality boundaries are explicitly 
stated.
Analysis of Variance (ANOVA)
An ANOVA model using PROC MIXED will be used to estimate the ratio of the PK parameter 
at each dose level to the PK parameter at the reference dose. The parameters will be 
dose-normalized and natural log-transformed prior to analysis. The reference dose is 1 mg, 
determined by the PK scientist. Dose normalization is calculated by dividing each PK parameter 
value by the test dose/reference dose ratio. The ratio of geometric least-squares means (GLSM) 
and the corresponding 90% CI will be estimated for each PK parameter of interest.
The statistical model will include dose as a fixed effect {U.S. Department of Health and Human 
Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) 
2003}, {U.S. Department of Health and Human Services Food and Drug Administration Center 
for Drug Evaluation and Research (CDER) 2001}. The following SAS PROC MIXED code will 
provide the single dose comparison analysis and the 90% CI calculations for the natural 
log-transformed normalized PK parameter Cmax. Similar code will be used for other natural 
log-transformed dose normalized PK parameters. The estimate statements assume that the
treatment is ordered as VES 1 mg, VES 2 mg, VES 4 mg, VES 6 mg, VES 8 mg, VES 10 mg 
and VES 12 mg.
y
1



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proc mixed;
  class dose;
  model lncmax = dose / ddfm=kr;
  lsmeans dose/cl alpha=0.1;
  estimate “VES 2 mg vs. 1 mg” dose -1 1 0 0 0 0 0/ cl alpha=0.10;
  estimate “VES 4 mg  vs. 1 mg” dose -1 0 1 0 0 0 0/ cl alpha=0.10;
  estimate “VES 6 mg  vs. 1 mg” dose -1 0 0 1 0 0 0/ cl alpha=0.10;
  estimate “VES 8 mg  vs. 1 mg” dose -1 0 0 0 1 0 0 / cl alpha=0.10;
  estimate “VES 10 mg  vs. 1 mg” dose -1 0 0 0 0 1 0/ cl alpha=0.10;
  estimate “VES 12 mg  vs. 1 mg” dose -1 0 0 0 0 0 1/ cl alpha=0.10;
  run;
The ESTIMATE statement is used to produce the point estimate and the corresponding 90% CI 
of the difference in PK parameters of interest on a logarithmic scale. The test-to-reference ratio 
and the 90% CI will be calculated by taking the exponential of the point estimate and the 
corresponding lower and upper limits.


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9.
REFERENCES
Smith BP, Vandenhende FR, DeSante KA, Farid NA, Welch PA, Callaghan JT, et al. Confidence 
interval criteria for assessment of dose proportionality. Pharm Res 2000;17 (10):1278-83.
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug 
Evaluation and Research (CDER). Guidance for Industry. Statistical Approaches to 
Establishing Bioequivalence.  January, 2001.
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug 
Evaluation and Research (CDER). Guidance for Industry. Bioavailability and 
Bioequivalence Studies for Orally Administered Drug Products - General Considerations 
(Revision 1).  March, 2003.


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10.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.
WinNonlin. Pharsight Corporation Version 6.3. Mountain View, CA.


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


VES (GS-9620)
GS-US-382-1450
Statistical Analysis Plan (Final Analysis) 
Version 1.0
CONFIDENTIAL
Page 36
15 May 2019
12.
APPENDICES 
Appendix 1.
PK Parameters
PK parameters evaluated in this study are listed below.
Parameter
Description
AUClast
area under the concentration versus time curve from time zero to the last quantifiable concentration
AUCinf
area under the concentration versus time curve extrapolated to infinite time, calculated as AUC0-last
(Clast/z)
%AUCexp
Percentage of AUC extrapolated between AUC0-last and AUCinf
Clast
last observed quantifiable concentration of the drug in plasma
Cmax
maximum observed concentration of drug in plasma
CL/F
apparent oral clearance after administration of the drug: 
at single dose: CL/F = Dose/AUCinf , where “Dose” is the dose of the drug
at steady state: CL/F = Dose/AUCtau, where “Dose” is the dose of the drug
T1/2
estimate of the terminal elimination half-life of the drug in plasma, calculated by dividing the 
natural log of 2 by the terminal elimination rate constant (z)
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
Vz/F
apparent volume of distribution of the drug
z
terminal elimination rate constant, estimated by linear regression of the terminal elimination phase 
of the plasma concentration of drug versus time curve
The following plasma PK parameters of VES will be calculated:
Cmax, Tmax, Clast, Tlast, z, T1/2, AUClast, AUCinf, %AUCexp, Vz/F, and CL/F.


VES (GS-9620) 
GS-US-382-1450 
Statistical Analysis Plan (Final Analysis) 
Version 1.0 
Appendix 2. 
Schedule of Assessments 
Study Procedures Table I Cohorts 1 to 3 
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Page 37 
15 May 2019 


VES (GS-9620) 
GS-US-382-1450 
Statistical Analysis Plan (Final Analysis) 
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Page 38 
15 May 2019 


VES (GS-9620) 
GS-US-382-1450 
Statistical Analysis Plan (Final Analysis) 
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Page 39 
15 May 2019 


VES (GS-9620) 
GS-US-382-1450 
Statistical Analysis Plan (Final Analysis) 
Version 1.0 
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Shipment Manual). 
CONFIDENTIAL 
Page40 
15 May 2019 
Q 
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VES (GS-9620) 
GS-US-382-1450 
Statistical Analysis Plan (Final Analysis) 
Study Procedures Table (Cohort 4) 
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Page41 
15 May 2019 


VES (GS-9620) 
GS-US-382-1450 
Statistical Analysis Plan (Final Analysis) 
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Page42 
15 May 2019 


VES (GS-9620) 
GS-US-382-1450 
Statistical Analysis Plan (Final Analysis) 
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h 
Details of pharmac-0kinetic blood sampling procedures and ample management for all PK samples in the study will be documented in the Phannacokinetic Sample 
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On dosing days study dmg should be taken with approxiniately 240 mL of water on an empty stomach. Food will not be penuitted between at least 2 hours prior to and until 
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CONFIDENTIAL 
Page43 
15 May 2019 
Q 
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VES (GS-9620) 
GS-US-382-1450 
Statistical Analysis Plan (Final Analysis) 
Study Procedures Table (Cohorts 5 to 9)3 
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15 May 2019 


VES (GS-9620) 
GS-US-382-1450 
Statistical Analysis Plan (Final Analysis) 
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Page45 
15 May 2019 


CCI
VES (GS-9620) 
GS-US-382-1450 
Statistical Analysis Plan (Final Analysis) 
Study Procedm·e• 
Whole blood ISG 
mRNA 
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RNA/DNA 
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15 May 2019 


CCI
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Statistical Analysis Plan (Final Analysis) 
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c 
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d 
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found to be safe, Dose 4 and subsequent Doses {5-10) will escalate to GS-9620 12 mg. If dose escalation is not approved by the SEC, subje.cts will continue receiving 10 mg 
of GS-9620 or placebo from Doses 4 to 10 
e 
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f 
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g 
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Ill -~--xamination as ne,eded 
• 
Females of childbearing potential only. Positive urine pregnancy tests will be con.fumed with a serum test at any visit. At End of Study visit, urine pregnancy test only 
pe1fonned if not done within past 30 days 
k 
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Collection, Processing, Storage, and Shipment Manual. 
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CONFIDENTIAL 
Page47 
15 May 2019 
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VES (GS-9620)
GS-US-382-1450
Statistical Analysis Plan (Final Analysis) 
Version 1.0
CONFIDENTIAL
Page 48
15 May 2019
Appendix 3.
Programming Specification
1) AGE calculated as follows:
a) AGE (years) is calculated from the number of days between the date of birth (DOB) 
and Day 1 (first dose date),
b) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
c) Divide the result in (b) by 12,
d) AGE = the integer of the result in (c),
e) If the DOB and Day 1 have the month in common and the birthday is later in the 
month than the date of Study Day 1, then subtract one from the AGE result above.
For subjects randomized and never dosed with study drug, age will be calculated from the 
date of randomization.
2) All screened subjects refer to all subjects who are screened (ie, with nonmissing 
screening date) and have a screening number. For summaries, the same subject is counted 
only once. DOB and other demographic information such as sex, race, ethnicity, country, 
and initials will be used to identify unique screened subjects.
3) Screen failure subjects are the subjects who are screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of 
protocol the subject was consent to. 
4) Subjects in the randomized analysis set are defined as subjects randomized into the study. 
IXRSRAND is the source to determine whether the subject is randomized (ie, subject 
with nonmissing RGMNDTN in the IXRSRAND dataset) and confirmed by the eCRF 
ENROLL dataset (ie, ENROLLYN = “Yes” in ENROLL dataset).
5) Randomized treatment (ie, TRT01P in ADSL) are derived from IXRSRAND, while 
actual treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment 
if subject took at least 1 dose of study drug and assigned as blank if subject never dosed.
6) In disposition table, the reasons for premature discontinuation are displayed in the order 
as they appear on the eCRF.


VES (GS-9620)
GS-US-382-1450
Statistical Analysis Plan (Final Analysis) 
Version 1.0
CONFIDENTIAL
Page 49
15 May 2019
7) Body mass index (BMI) and Body Surface Area (BSA)
BMI and BSA will be calculated only at baseline as follows:
BMI = (weight [kg]) / (height [meters]2)
BSA (m2) = SQRT( [Height(cm) × Weight(kg) ] / 3600 )
Baseline height and weight will be used for this calculation. 
8) Please note, “Not Permitted”, “Unknown”, or missing categories will be excluded for 
percentage calculation. Except for Mode of infection (HIV Risk Factors), where 
“Unknown” will be included for percentage calculation, since a subject may fit more than 
1 HIV risk factors, therefore percentage may add to more than 100% and no p-value will 
be generated. 
Subjects with Race = “Not Permitted” will also be excluded to define Race subgroup 
(ie, black vs. nonblack) for efficacy subgroup analysis. 
9) Last Dose Date and Last Study Date
a) Last Dose Date (ie, TRTEDTC, TRTEDT, TR01EDT or TR01EDTC) in ADSL was 
defined in Section 3.8.1.
For subjects with a partial last dosing date (ie, month and year of last dose are 
known), the latest of the dispensing dates of study drug bottles, study drug start dates 
and end dates, and the imputed last dose date [day imputed as 15] will be used as the 
final imputed last dose date. However if dispensing date’s month is after last dose 
date’s month, data query is needed.
If subject died and the death date is complete (ie, not partial date) and before the 
imputed last dose date, the complete death date should be used as the imputed last 
dose date. 
b) Last Study Date is the latest of the study drug start dates and end dates, the clinic visit 
dates, and the laboratory visit dates, including the 30-day follow-up visit date, for 
subjects who prematurely discontinued study or who completed study according to 
the Study Completion eCRF. If study drug start dates or end date is partially missing 
(ie, only year and month are known), the day will be imputed as 15 for the purpose of 
this analysis.
If subject died and the death date is complete (ie, not partial date) and before the 
imputed last study date, the complete death date should be used as the imputed last 
study date. 


VES (GS-9620)
GS-US-382-1450
Statistical Analysis Plan (Final Analysis) 
Version 1.0
CONFIDENTIAL
Page 50
15 May 2019
10) Toxicity Grades:
a) For toxicity grade summaries, include all postbaseline graded results up to 30 days 
after the last dose of study drug, not just those used in by-visit summaries.
b) For glucose grading,the treatment-emergent flag cannot be determined for nonfasting 
glucose (including glucose results without a known fasting status). As a result, these 
records will be excluded from the “Maximum Treatment-emergent Toxicity Grade” 
summary in the “Treatment-emergent Laboratory Abnormalities” or “Treatment-
emergent Grade 3 or 4 Laboratory Abnormalities” summary tables. In addition, 
fasting glucose and nonfasting glucose will be listed as two separate laboratory tests 
in the “Laboratory Abnormalities” and “Grade 3 or 4 Laboratory Abnormalities” 
listings. Only a maximum postbaseline toxicity flag will be displayed and the 
treatment-emergent flag will not be displayed for nonfasting glucose as the 
treatment-emergent flag cannot be determined for nonfasting glucose. 
11) TEAE
Events with Missing Onset Day and/or Month
An AE is treatment emergent if the following 3 criteria are met:

The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and

The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and

End date is as follows: 
a.
The (complete) end date is on or after the first dose date, or
b. The month and year (or year) of end date is the same or after the month and 
year (or year) of the first dose of study drug, or
c.
End date is completely missing 
Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of 
the criteria specified in 3) above.


VES (GS-9620)
GS-US-382-1450
Statistical Analysis Plan (Final Analysis) 
Version 1.0
CONFIDENTIAL
Page 51
15 May 2019
12) PK parameters at the individual subject level should be displayed with the following 
reported number of decimal places:

LambdaZ, r2, r2 adj, and CORRXY: 3 decimal places

t1/2, Tlast, Tmax, BEGHOUR, and ENDHOUR: 2 decimal places

AUCtau, AUC0-last, AUCinf, %otAUCexp, Vz/F, CL/F, CLss/F, Cmax, Clast and Ctau: 
1 decimal place

NPOINTS: 0 decimal place

PK concentration data will be reported with 1 decimal place. 
13) Concomitant nonstudy-drug ARV medications (ie, ARV medications other than study 
drug that are taken while receiving study drug) will be flagged in “Nonstudy-Drug 
Antiviral Medication” listing. The logic to define concomitant nonstudy-drug ARV is
similar to concomitant non-ARV Medications (see details in Section 7.4.3)
14) For biomarker data, study day will be calculated from the first dosing date of study drug 
and derived as follows:
For postdose study days: Collection Date – First Dosing Date + 1
For days prior to the first dose: Collection Date – First Dosing Date
Therefore, study day 1 is the day of first dose of study drug administration.
15) The duration of being diagnosed with HIV disease (in years) is calculated as (first dose 
date - date subject was diagnosed with HIV disease)/365.25. The duration of ARV prior 
to study (in years) is calculated as (first dose date - date subject first start ARV)/365.25. 
For the date subject was diagnosed with HIV disease and date subject first start ARV, 
missing dates will be imputed. If only the date is missing, it is imputed as 15. If both 
month and date are missing, it will be imputed as July 1st.


GS-382-1450 Final Analysis SAP
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical Research eSigned 15-May-2019
18:35:04
Biostatistics eSigned
15-May-2019
19:30:18
PPD
PPD