A Phase 1, Open-Label, Single-Dose Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, GSK3810109, Administered Either Subcutaneously or Intravenously With Recombinant Human Hyaluronidase PH20 (rHuPH20) to Healthy Adults
Phase: PHASE1
Conditions: HIV Infections
Sponsor: ViiV Healthcare

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ViiV healthcare and GlaxoSmithKline group of companies 
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TITLE PAGE 
Protocol Title: A Phase 1, Open-Label, Single-Dose Study of the Safety and 
Pharmacokinetics of a Human Monoclonal Antibody, GSK3810109, Administered Either 
Subcutaneously with Recombinant Human Hyaluronidase PH20 (rHuPH20) or 
Intravenously, to Healthy Adults 
Protocol Number: 217901/Amendment 02 
Compound Number or Name: 
GSK3810109  
Study Phase: Phase 1 
Brief Title: A study to investigate the safety and pharmacokinetics of a single dose of 
GSK3810109 administered either subcutaneously with rHuPH20 or intravenously, in 
healthy adult participants 
Sponsor Name and Legal Registered Address (excluding US): 
ViiV Healthcare UK Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
US IND Sponsor Name and Legal Registered Address: 
ViiV Healthcare Company 
Five Moore Drive 
P.O. 13398 
Research Triangle Park,  
NC 27709-3398, 
USA 
Telephone: + 1 919 438 2100 
 
Regulatory Agency Identifying Number(s):US IND: 148241 
 
Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual. 
 
Sponsor Signatory 
Scott McCallister, Head Physician 
ViiV Healthcare and Development 
Approval Date: 26 Sep 2022 
©2022 ViiV Healthcare and GSK group of companies or its licensor. All rights 
reserved.  Unauthorized copying or use of this information is prohibited.

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Document Identifier 
Amendment 02 
26 Sep 2022 
TMF- 14965235 
Amendment 01 
03 June 2022 
TMF-14645038 
Original Protocol 
25 January 2022 
TMF-14419933 
 
Amendment 02: 26 Sep 2022 
Overall Rationale for the Amendment: The protocol is amended to include an 
additional dosing group 
 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
Throughout the 
document, as 
applicable  
• Sections were modified to 
accommodate additional 
subcutaneous dosing group, 
designated as Part 3 of the 
study 
• 
Section 1.6 
Schedule of Activities 
(SoA) Part 2 
• Modified SoA for Part 2 to correct 
headers, include 
electrocardiogram (ECG) at 
end of infusion, and to add 
missing elements 
• Increased frequency of clinical 
laboratory monitoring (Day 2 
through Day 8 while in the 
clinic) in SoA for Part 2 
• SoA of Part 2 of the study has 
been identified to have incorrect 
headers, formatting errors, and 
missing elements from the list of 
clinical activities.  
• As per FDA feedback to increase 
frequency of clinical laboratory 
monitoring because there are no 
clinical data with doses of 
GSK3810109 greater than 40 
mg/kg as a single administration. 
Section 1.1 Synopsis  
Safety Review Team composition 
To reflect correct composition as 
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Section # and Name 
Description of Change 
Brief Rationale 
was modified 
mentioned in Section 10.1.5 
Section 1.5 
Schedule of Activities 
(SoA) Part 1 
Part 1 SoA corrected to remove 
footnote number for predose ECG 
and footnote number for HIV and 
hepatitis B and C was updated 
Errors inadvertently introduced in 
Amendment 1 were corrected. 
Section 1.6 Schedule 
of Activities (SoA) 
(Part 2) 
 
Notes section 
This section was added to provide 
clarity on activities for Part 2 study 
assessments 
Section 4.1 Overall 
Design 
Dose definition at dose of 2000 
U/mL or ~28,000 U for a 70 kg 
participant was added 
Added clarification on the dosing  
Section 5.2 
Exclusion criteria 
Exclusion criterion of positive 
hepatitis C antibody test was 
added 
 
This exclusion criterion was not 
previously included, although the 
hepatitis C antibody test was 
performed by the clinic and a 
negative result was required prior to 
study entry. 
Throughout the 
document 
Minor formatting, administrative, 
and language changes were 
made 
For clarity and better readability 
 

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TABLE OF CONTENTS 
PAGE 
1. 
PROTOCOL SUMMARY .......................................................................................... 7 
1.1. 
Synopsis ....................................................................................................... 7 
1.2. 
Schema (Part 1) .......................................................................................... 14 
1.3. 
Schema (Part 2) .......................................................................................... 15 
1.4. 
Schema (Part 3) .......................................................................................... 16 
1.5. 
Schedule of Activities (SoA) Part 1 ............................................................. 17 
1.6. 
Schedule of Activities (SoA) (Part 2) ........................................................... 21 
1.7. 
Schedule of Activities (SoA) Part 3 ............................................................. 25 
2. 
INTRODUCTION .................................................................................................... 29 
2.1. 
Study Rationale .......................................................................................... 30 
2.2. 
Background ................................................................................................ 31 
2.2.1. 
GSK3810109 ............................................................................... 31 
2.2.2. 
Recombinant Human Hyaluronidase PH20 (rHuPH20) ................ 32 
2.3. 
Benefit/Risk Assessment ............................................................................ 33 
2.3.1. 
Risk Assessment ......................................................................... 33 
2.3.2. 
Benefit Assessment ..................................................................... 44 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 44 
3. 
OBJECTIVES AND ENDPOINTS AND/OR ESTIMANDS ....................................... 45 
4. 
STUDY DESIGN .................................................................................................... 51 
4.1. 
Overall Design ............................................................................................ 51 
4.2. 
Scientific Rationale for Study Design .......................................................... 53 
4.3. 
Justification for Dose .................................................................................. 54 
4.4. 
End of Study Definition ............................................................................... 56 
5. 
STUDY POPULATION ........................................................................................... 56 
5.1. 
Inclusion Criteria ......................................................................................... 56 
5.2. 
Exclusion Criteria ........................................................................................ 58 
5.3. 
Lifestyle Considerations .............................................................................. 60 
5.3.1. 
Meals and Dietary Restrictions .................................................... 60 
5.3.2. 
Caffeine, Alcohol, and Tobacco ................................................... 60 
5.3.3. 
Activity ......................................................................................... 60 
5.4. 
Screen Failures........................................................................................... 60 
5.5. 
Criteria for Temporarily Delaying ................................................................ 61 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 61 
6.1. 
Study Interventions Administered ............................................................... 61 
6.2. 
Study Product Administration ...................................................................... 62 
6.3. 
Preparation, Handling, Storage and Accountability ..................................... 63 
6.4. 
Measures to Minimize Bias: Randomization and Blinding ........................... 63 
6.5. 
Study Intervention Compliance ................................................................... 64 
6.6. 
Overdose .................................................................................................... 64 
6.7. 
Concomitant Therapy.................................................................................. 64 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 65 

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7.1. 
Discontinuation of Study Intervention .......................................................... 65 
7.2. 
Liver Chemistry Stopping Criteria ............................................................... 66 
7.3. 
QTcF Stopping Criteria ............................................................................... 66 
7.4. 
Participant Discontinuation/Withdrawal from the Study ............................... 66 
7.5. 
Lost to Follow Up ........................................................................................ 67 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 67 
8.1. 
Safety Assessments ................................................................................... 68 
8.1.1. 
Physical Examinations ................................................................. 68 
8.1.2. 
Vital Signs .................................................................................... 68 
8.1.3. 
Electrocardiograms ...................................................................... 68 
8.1.4. 
Clinical Safety Laboratory Tests .................................................. 69 
8.1.5. 
Pregnancy Testing ....................................................................... 69 
8.1.6. 
COVID-19 Measures ................................................................... 69 
8.2. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ......................................................................................... 70 
8.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 70 
8.2.2. 
Method of Detecting AEs and SAEs ............................................. 70 
8.2.3. 
Follow-up of AEs and SAEs ......................................................... 71 
8.2.4. 
Regulatory Reporting Requirements for SAEs ............................. 71 
8.2.5. 
Pregnancy ................................................................................... 71 
8.2.6. 
Adverse Events of Special Interest .............................................. 72 
8.2.7. 
Specific Toxicities/Adverse Event Management ........................... 72 
8.3. 
Pharmacokinetics ....................................................................................... 73 
8.4. 
Genetics ..................................................................................................... 74 
8.5. 
Immunogenicity Assessments ..................................................................... 74 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 74 
9.1. 
Statistical Hypotheses................................................................................. 74 
9.1.1. 
Multiplicity Adjustment ................................................................. 74 
9.2. 
Analysis Sets .............................................................................................. 75 
9.3. 
Statistical Analyses ..................................................................................... 76 
9.3.1. 
General Considerations ............................................................... 76 
9.3.2. 
Primary Endpoints/Estimands Analysis ........................................ 76 
9.3.3. 
Secondary Endpoints/Estimands Analysis ................................... 76 
9.3.4. 
Exploratory Endpoints/Estimands Analysis .................................. 78 
9.4. 
Interim Analysis .......................................................................................... 78 
9.5. 
Sample Size Determination ........................................................................ 78 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 79 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 79 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 79 
10.1.2. 
Financial Disclosure ..................................................................... 79 
10.1.3. 
Informed Consent Process .......................................................... 80 
10.1.4. 
Data Protection ............................................................................ 80 
10.1.5. 
Committees Structure .................................................................. 81 
10.1.6. 
Dissemination of Clinical Study Data ........................................... 81 
10.1.7. 
Data Quality Assurance ............................................................... 81 
10.1.8. 
Source Documents ...................................................................... 82 

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10.1.9. 
Study and Site Start and Closure ................................................. 83 
10.1.10. Publication Policy ......................................................................... 84 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 85 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 87 
10.3.1. 
Definition of AE ............................................................................ 87 
10.3.2. 
Definition of SAE .......................................................................... 89 
10.3.3. 
Recording and Follow-up of AEs and SAEs ................................. 90 
10.3.4. 
Reporting of SAE to ViiV/GSK ..................................................... 92 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ....................................... 94 
10.4.1. 
Definitions: ................................................................................... 94 
10.4.2. 
Contraception Guidance: ............................................................. 95 
10.4.3. 
Collection of Pregnancy Information: ........................................... 96 
10.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments .............................................................................................. 98 
10.6. 
Appendix 6: COVID-19 Pandemic and Clinical Study Continuity ............... 100 
10.6.1. 
Changes to Study Visits and Study Procedures ......................... 100 
10.6.2. 
Changes to Informed Consent ................................................... 101 
10.6.3. 
COVID-19 Vaccines ................................................................... 101 
10.6.4. 
COVID-19 Experimental Agents ................................................ 101 
10.6.5. 
COVID-19 Specific Data Capture ............................................... 102 
10.7. 
Appendix 7: Division of AIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events Corrected Version 2.1, July 2017 ............... 105 
10.8. 
Appendix 8: Numeric Rating Scale............................................................ 106 
10.9. 
Appendix 9: PIN Questionnaire (For Part 1 and Part 3 only) ..................... 107 
10.10. Appendix 10: Abbreviations and Trademarks ............................................ 113 
10.11. Appendix 11: Protocol Amendment History ............................................... 116 
11. REFERENCES ..................................................................................................... 117 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase 1, Open-Label, Single-Dose Study of the Safety and 
Pharmacokinetics of a Human Monoclonal Antibody, GSK3810109, Administered Either 
Subcutaneously with Recombinant Human Hyaluronidase PH20 (rHuPH20) or 
Intravenously, to Healthy Adults 
Brief Title: A study to investigate the safety and pharmacokinetics of a single dose of 
GSK3810109 administered either subcutaneously with rHuPH20 or intravenously, in 
healthy adult participants. 
Rationale: GSK3810109 is a human monoclonal antibody active against human 
immunodeficiency virus (HIV) that can mediate extraordinary breadth and potency 
against various HIV isolates, including strains traditionally resistant to other antibodies in 
this class.  
This study is designed to evaluate safety, tolerability, and pharmacokinetic (PK) 
endpoints in healthy adult participants when GSK3810109 is administered as either 
subcutaneous (SC) injection (Part 1 and Part 3 of study) or by intravenous (IV) infusion 
(Part 2 of study). Dosing by either SC or IV infusion may each offer practical advantages 
related to tolerability, simplicity, or frequency of dosing in the administration of 
GSK3810109. 
Administration by SC Infusion 
While broadly neutralizing antibodies have typically been administered at doses requiring 
IV infusions, the potency of GSK3810109 may enable lower doses of the antibody to 
mediate an effect. The ability to administer GSK3810109 as a SC injection may offer 
several advantages over IV infusion, including fewer complications, less pain, and ease 
of administration, especially with chronic dosing. 
The rHuPH20 enzyme facilitates SC delivery of co‐administered therapeutics. 
Hyaluronidase injection is effective for use as an adjunct to increase the absorption and 
dispersion of other injected drugs, including for hypodermoclysis and as an adjunct in SC 
urography for improving the resorption of radiopaque agents. The use of rHuPH20 with 
GSK3810109 offers the potential to administer a larger volume of the antibody than 
could be administered alone (~2.0 mL). The current study will investigate the ability to 
deliver a larger SC dose of GSK3810109 (20 mg/kg, up to 24 mL [Part 1] or 
 
 in combination with rHuPH20. The rHuPH20 will be co-mixed with 
GSK3810109 at a concentration of 2000 U/mL based on the dosing volume of 
GSK3810109 (variable dose/volume of rHuPH20 for the 20 mg/kg dose level; 
 
 Thus, for Part 1, the maximum volume needed to 
administer a SC dose is not expected to exceed 24 mL. For Part 3, 
 
 
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Administration by IV Infusion 
There is a practical limitation for administration of high doses of GSK3810109 via SC 
infusion. To date, the maximum dose administered via SC route is 20 mg/kg in 
combination with rHuPH20, while an IV route allows higher dose administration. In this 
study, an IV dose of 60 mg/kg of GSK3810109 will be administered, which offers the 
potential for an ultra-long-acting target profile to support administration every 4 to 
6 months, thus reducing dosing frequency and potentially improving adherence and 
acceptability. Medication adherence and decreasing frequency of clinic visits is the most 
important determinant for sustained viral suppression and long-term treatment success. 
GSK3810109 dose has not exceeded 40 mg/kg in humans as a single administration. 
Pharmacokinetic modeling suggests a 60 mg/kg dose may be adequate for every 4 to 
6 months administration. The no-observed-adverse-effect level (NOAEL) set by the 
Vaccine Research Center (VRC) is at 400 mg/kg IV and was endorsed by the FDA. 
Based on the same VRC generated data, ViiV Healthcare set the NOAEL at 40 mg/kg 
based on the morbidity of one male rat at 400 mg/kg, for which it was not possible to 
exclude a relationship to exposure. 
A review of observed GSK3810109 Cmax and area under the plasma concentration-time 
curve (AUC) exposure in humans at 40 mg/kg IV found levels to be appreciably higher 
than rodent exposures at the GSK/ViiV 40 mg/kg NOAEL. This suggests the rodent 
NOAEL set at 40 mg/kg may be less relevant in humans as a maximum ceiling dose. In 
addition, simulated PopPK modeling show that 60 mg/kg IV in humans are predicted to 
have a lower Cmax than the VRC 400 mg/kg rat NOAEL Cmax. 
The inclusion of both routes of administration in this study is an efficient design to enable 
rapid progression to future studies using either 1 or both routes of administration. 
Objectives and Endpoints and Estimands: 
Objectives 
Endpoints 
Primary 
 
• To evaluate the safety and tolerability of a 
single dose of GSK3810109 administered 
SC with rHuPH20 or IV in healthy adult 
participants 
Part 1 and Part 3 (SC injection) 
• The number and percentages of participants 
who have AEs (Grade 2 or higher) and SAEs 
following GSK3810109 SC administration 
through Week 24 
• The number and percentages of participants 
who have ISRs within 7 days following 
GSK3810109 SC administration 
• The incidence of Grade 2 to 4 elevated 
ALT/AST following GSK3810109 SC 

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Objectives 
Endpoints 
administration  
Part 2 (IV infusion)  
• The number and percentages of participants 
who have AEs and SAEs following 
GSK3810109 IV administration through 
Week 24  
• The incidence of Grade 2 to 4 elevated 
ALT/AST following GSK3810109 IV 
administration through Week 24 
Secondary 
 
• To evaluate the PK of a single dose of 
GSK3810109 administered SC with 
rHuPH20 or IV in healthy adult participants  
• Assessment of GSK3810109 PK parameters 
including AUC(0-inf), AUC(0-t), Cmax, Tmax, 
and t1/2 (if possible) 
• To assess the severity and acceptance of 
pain and ISRs after SC administration of 
GSK3810109 with rHuPH20  
• Dimension score “acceptance of ISRs” and 
individual item score assessing pain at Day 2 
and Day 7 using the PIN Questionnaire  
• Proportion of participants who are bothered 
or affected by the pain and local reactions as 
a result of the injection as measured by the 
PIN on Days 2 and 7 
• Post-injection pain assessment using NRS at 
Days, 1, 2, and 7 
• The incidence and duration of ISRs 
assessed overall and by grade including the 
duration at grade 
• To assess the severity of pain after IV 
administration of GSK3810109 
• Post-infusion pain assessment using NRS 
at Days, 1, 2, and 7 
• To evaluate additional safety parameters 
following administration of GSK3810109 SC 
with rHuPH20 or IV in healthy adult 
participants 
• Change from baseline in clinical laboratory 
assessments, ECGs, and vital sign 
measurements 
Exploratory 
 
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Objectives 
Endpoints 
; AE = adverse event; ALT = alanine aminotransferase; AST = aspartate 
aminotransferase; AUC(0-inf) = area under the plasma concentration-time curve from time zero extrapolated to 
infinity; AUC(0-t) = area under the plasma concentration-time curve from time zero to time of last observed 
quantifiable concentration; Cmax = maximum observed concentration; ECG = electrocardiogram; ISR = injection 
site reaction; IV = intravenous (ly) NRS = Numeric Rating Scale; PIN = Perception of Injection; 
PK = pharmacokinetics; SAE = serious adverse event; SC = subcutaneous (ly); t1/2 = apparent terminal phase 
half-life; Tmax = time of maximum observed concentration. 
Overall Design: 
This is an open-label, single-dose study to assess the safety, tolerability, and PK of 
GSK3810109 administered SC with rHuPH20 or IV in healthy adult participants 
This study will comprise 3 parts:  
In Part 1, approximately 8 participants will receive a single 20 mg/kg SC dose of 
GSK3810109 co-administered with rHuPH20 at a dose of 2000 U/mL or ~28,000 U for a 
70 kg participant. The participants will be admitted in the clinic on Day –1 and the study 
product will be administered on Day 1. The participants will remain in the clinic for 
approximately 8 hours for study-related procedures after study product administration 
and will be followed up for 24 weeks.  
Safety laboratory samples will be collected throughout the study as per the Schedule of 
Activities (SoA). The primary endpoint of injection site reaction (ISR) will be evaluated 
at specified time points up to Day 7; study participants will keep a diary of ISRs for 
14 days after study product administration. Symptoms, maximum intensities, and 
durations will be reported through end of study to characterize presentation and 
resolution of local ISRs. 
In Part 2, approximately 8 participants will receive a single 60 mg/kg IV dose of 
GSK3810109. A sentinel cohort of 2 participants will be used to mitigate the risk of 
unexpected AEs prior to dosing of the remaining 6 participants, who will be dosed in 
sequential cohorts of 2 participants each. 
The sentinel cohort of 2 participants will be admitted to the clinic on Day –1. The study 
product will be administered on Day 1 and participants will remain in the clinic and be 
monitored for 7 days after study product administration. The participants will be 
discharged from the clinic on Day 8 and will be followed up for 24 weeks. 
Following Day 10 visit, core Safety Review Team (SRT) will review the safety data 
(safety laboratory data, electrocardiogram, and AEs) from the sentinel cohort and may 
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recommend continuation of the study where the next cohort of 2 participants will be 
dosed. 
The second cohort of 2 participants will be admitted to the clinic on Day –1. The study 
product will be administered on Day 1 and participants will remain in the clinic and be 
monitored for 7 days after study product administration. The participants will be 
discharged from the clinic on Day 8 and will be followed up for 24 weeks. A review of at 
least AE data from this cohort will be conducted after a minimum of 4 days following 
infusion of GSK3810109 and the core SRT may recommend continuation of the study 
where the next cohort of 2 participants will be dosed. 
The third cohort of 2 participants will be admitted to the clinic on Day –1. The study 
product will be administered on Day 1 and participants will remain in the clinic and be 
monitored for 7 days after study product administration. The participants will be 
discharged from the clinic on Day 8 and will be followed up for 24 weeks. A review of at 
least AE data from this cohort will be conducted after a minimum of 4 days following 
infusion of GSK3810109 and the core SRT may recommend continuation of the study 
into the fourth cohort of 2 participants. 
The fourth cohort of 2 participants will be admitted to the clinic on Day –1. The study 
product will be administered on Day 1 and participants will remain in the clinic and 
monitored for 7 days after study product administration. The participants will be 
discharged from the clinic on Day 8 and will be followed up for 24 weeks. 
Safety laboratory samples will be collected throughout the study as per the SoA. 
 
 An 
initial cohort of 2 participants will be used to mitigate the risk of unexpected AEs prior to 
dosing of the remaining 6 participants.  
In the first cohort, 2 participants will be admitted in the clinic on Day –1 and the study 
product will be administered on Day 1. The participants will remain in the clinic and be 
monitored for 3 days after study product administration. The participants will be 
discharged from the clinic on Day 4 and will be followed up for 24 weeks. Following 
discharge, core SRT will review at least AE data and may recommend continuation of the 
study where the next cohort of 6 participants will be dosed. 
The second cohort of 6 participants will be admitted to the clinic on Day –1. The study 
product will be administered on Day 1 and participants will remain in the clinic and be 
monitored for 3 days after study product administration. The participants will be 
discharged from the clinic on Day 4 and will be followed up for 24 weeks. 
Safety laboratory samples will be collected throughout the study as per the SoA. The 
primary endpoint of ISR will be evaluated at specified time points up to Day 7; study 
participants will keep a diary of ISRs for 14 days after study product administration. 
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Symptoms, maximum intensities, and durations will be reported through end of study to 
characterize presentation and resolution of local ISRs. 
Note: Results of Part 3 will be reported separately from Part 1 and Part 2. 
Interim Analysis 
An interim analysis is planned after all participants receiving SC administration in Part 1 
complete their Week 24 visit. At that time point, the data available for participants 
receiving IV administration will also be analyzed and included. 
Brief Summary: 
The purpose of this study is to assess the safety, tolerability, and PK of a single 20 mg/kg 
or 
 or a single 
60 mg/kg IV dose of GSK3810109, in healthy adult participants. 
• Study duration: Up to 24 weeks excluding screening 
• Treatment duration:  
o For Part 1, single SC infusion on Day 1 that is expected to take 3 to 
15 minutes to administer.  
o For Part 2, single IV infusion on Day 1, that is expected to take 
approximately 60 minutes to administer; the entire infusion should not 
exceed 2 hours. 
o 
Number of Participants: 
A sufficient number of participants will be enrolled to ensure that approximately 
8 participants complete each part of the study for a total of approximately 24 participants 
in the study. 
Participants who withdraw prior to study completion may be replaced. 
Note: Enrolled means a participant’s agreement to participate in a clinical study 
following completion of the informed consent process and all screening activities. 
Potential participants who are screened for the purpose of determining eligibility for the 
study, but do not participate in the study, are not considered enrolled. A participant will 
be considered enrolled if the informed consent is not withdrawn prior to participating in 
any study activity after screening. 
Intervention Groups and Duration: 
The study duration will be 24 weeks (excluding screening) and the study product will be 
administered on Day 1 of each part.  
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Data Monitoring/ Other Committee: No Data and Safety Monitoring Board will be 
empaneled for this study 
An SRT for GSK3810109 reviews emerging and cumulative data for GSK3810109 on a 
monthly basis. For Part 1, safety review decisions and the status of the enrollment process 
will be shared with an SRT at regular intervals and discussed during the monthly SRT 
meetings.  
For Part 2, a core SRT for Study 217901 will review data for both sentinel and 
non-sentinel participants of the study. 
 
 The core SRT is 
composed of safety lead, medical monitors, and project biostatistician. 
The SRT will make recommendations to the ViiV Safety and Labelling Committee 
(VSLC) regarding safety findings, including study pause, modification, and termination. 
The VSLC is chaired by the ViiV Chief Medical Officer and will have the final decision 
on study modifications, including termination. Details regarding the VSLC membership 
and function are included within the VSLC Charter.
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1.2. 
Schema (Part 1) 
 

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1.3. 
Schema (Part 2) 
 
 
 

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1.4. 
Schema (Part 3) 
 
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1.5. 
Schedule of Activities (SoA) Part 1  
Visit Number 
 
01 
01A 01B 01C 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
ED = early 
discontinuation/withdrawal 
Time From Start of SC Infusion 
 
Pre SOI 4hr 8hr 24hr 48hr 72hr Wk1 Wk2 Wk3 Wk4 Wk8 Wk12 Wk16 Wk20 Wk24 
 
Day of Study1 
D-1 
D1 
D1 
D1 D1 
D2 
D3 
D4 
D7 D14 D21 D28 D56 D84 D112 D140 
D168 
 
Clinical Activity 
Screen 
Days 
-21 to -2 
Check-
in 
Intervention Period 
Follow-up 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to clinic 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge from clinic 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, weight, and BMI2 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs3 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination4 
X 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X  
Drug Alcohol/Cotinine /history 
and screen5 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Visit Number 
 
01 
01A 01B 01C 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
ED = early 
discontinuation/withdrawal 
Time From Start of SC Infusion 
 
Pre SOI 4hr 8hr 24hr 48hr 72hr Wk1 Wk2 Wk3 Wk4 Wk8 Wk12 Wk16 Wk20 Wk24 
 
Day of Study1 
D-1 
D1 
D1 
D1 D1 
D2 
D3 
D4 
D7 D14 D21 D28 D56 D84 D112 D140 
D168 
 
Clinical Activity 
Screen 
Days 
-21 to -2 
Check-
in 
Intervention Period 
Follow-up 
 
Past and Current medical 
conditions 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study product administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PIN and NRS6 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
12-lead ECG7 
X 
 
X 
 
X 
 
X 
X 
X 
X 
 
 
X 
 
 
 
 
X 
 
Clinical laboratory5 
X 
X 
 
 
 
 
X 
 
 
X 
X 
 
X 
 
 
X 
 
X 
X 
Urinalysis5 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Pregnancy test:(serum) 
(POCBP only)8 
X 
X 
 
 
 
 
X 
 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
FSH9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV and hepatitis B and C5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test for SARS-CoV-210 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Visit Number 
 
01 
01A 01B 01C 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
ED = early 
discontinuation/withdrawal 
Time From Start of SC Infusion 
 
Pre SOI 4hr 8hr 24hr 48hr 72hr Wk1 Wk2 Wk3 Wk4 Wk8 Wk12 Wk16 Wk20 Wk24 
 
Day of Study1 
D-1 
D1 
D1 
D1 D1 
D2 
D3 
D4 
D7 D14 D21 D28 D56 D84 D112 D140 
D168 
 
Clinical Activity 
Screen 
Days 
-21 to -2 
Check-
in 
Intervention Period 
Follow-up 
 
Timed PK sample11 
 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 sample 
collection 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Recording of injection site 
reactions in 14 days diary 
card12 
 
 
 
 
 
 
 
 
 
 
 
 
Recording of AEs/SAEs13 
 
 
 
 
X 
Concomitant medication 
review 
 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE = adverse event; BMI = body mass index; COVID‑19 = coronavirus disease; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus-1; ISR = injection site 
reaction; NRS = Numeric Rating Scale; PIN = Perception of Injection PK = pharmacokinetic(s); POCBP = participant of childbearing potential; SAE = serious adverse event; SARS-
CoV-2 = severe acute respiratory syndrome-related coronavirus-2; SC = subcutaneous; SOI = start of infusion 
Visit windows: Schedule Visits 01 through 13 with respect to Day 1. Visit 01 (-10 minutes for PK sample collection and vitals; -1 hour for ECG), Visit 01A (+10 minutes); Visits 01B and 
01C (±10 minutes); Visits 02, 03, and 04 (±6 hours); Visits 05, 06, 07, and 08 (±2 days), and Visits 09, 10, 11, 12, and 13 (±7 days). 
 
1 
Day 1 = day of product administration. The screening period will preferably be 14 days but may be extended to 21 days to allow for the possibility of study pauses or scheduling 
difficulty with the approval of the investigator. Day 1 evaluations prior to product administration will be considered as baseline for assessing subsequent AEs. [Note: Participants 
will remain in the clinic for approximately 8 hours for study-related procedures after study product administration]. 
2 
 Height and weight will be measured and BMI will be calculated at Screening. Only weight will be measured at Check-in and Day 1. 
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3 
Vital signs will include body temperature, systolic and diastolic blood pressure, respiratory rate, and pulse. The Oxygen saturation (SPO2) will also be measured during the in-clinic 
period on Day 1. For further details, refer to Section 8.1.2. 
4 
A full physical examination will be performed at Screening (at minimum, assessment of skin, head, ears, eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular system, 
abdomen, lymph nodes, and musculoskeletal system/extremities). A brief physical examination (at minimum, assessment of skin, lungs, cardiovascular system, and abdomen 
[liver and spleen]) will be performed at Check-in, at Day 1 (predose), at 8 hours, and at ED visit. Interim physical examinations may be performed at the discretion of the 
investigator, if necessary, to evaluate AEs or clinical laboratory abnormalities. 
5 
A complete list of assessments is provided in Section 10.2. 
6 
NRS will be administered on Day 1 at the end of the infusion. Additionally, PIN and NRS will be administered on Day 2 and Day 7. 
7 
The electrocardiogram (ECG) taken at Screening and on Day 1 before product administration will be a single reading; however, repeat ECGs are allowed at investigator’s 
discretion to confirm the eligibility. Triplicate 12-lead ECGs will be obtained for all postdose time points.  
8 
At the Day –1 visit, a serum sample will be sent for pregnancy testing. Pregnancy testing will be conducted on POCBP only on serum samples. Refer to Section 8.1.5. 
9 
Females with at least 12 months of amenorrhea must have a serum FSH test performed at Screening to confirm postmenopausal status.  
10 The clinic will follow their standard procedures and/or local guidelines with respect to COVID‑19 testing at Screening, enrollment, and any other time points during the study, if 
deemed necessary by the investigator. 
11 The PK blood draw “visits” are defined relative to the exact time of the end of infusion. The exact start and end times of product administration and the time of PK blood draw(s) 
will be recorded to ensure accurate PK analysis. All participants will be observed for 4 hours after product administration. 
12 An ISR that is considered Grade 3 or greater may be referred for dermatology consult and workup (dermatology referral for Grade 3 erythema without other local symptoms will be 
at the discretion of the investigator). Please refer to Section 8.2.7.1 for further details. 
13 Please refer to Section 8.2.1 for study participation related SAEs. 
 
Notes 
• 
The timing of planned study assessments may change during the course of the study based on emerging data/in-stream data review (e.g., to obtain data closer to the time of 
peak plasma concentrations) to ensure appropriate monitoring. 
• 
Any changes in the timing of time points for any planned study assessments as the result of emerging pharmacokinetic/pharmacodynamic data from this study must be 
documented and approved by the relevant study team member and then archived in the sponsor and site study files but will not constitute a protocol amendment. 
• 
The Competent Authority (CA) and ethics committee (EC) will be informed of any safety issues that constitute a substantial amendment and require alteration of the safety 
monitoring scheme or amendment of the informed consent form (ICF). The changes will be approved by the CA and the EC before implementation. 

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1.6. 
Schedule of Activities (SoA) (Part 2) 
Visit Number 
 
01 
01A 01B 01C 02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
ED = early 
discontinuation/withdrawal 
Time From Start of IV Infusion 
 
Pre EOI 4hr 8hr 24hr 48hr 72hr Wk1 Wk2 Wk2 Wk2 Wk3 Wk4 Wk8 Wk12 Wk16 Wk20 Wk24 
 
Day of Study1 
D-1 
D1 
D1 D1 D1 D2 D3 D4 D7 D8 D102 D14 D21 D28 D56 D84 D112 D140 
D168 
 
Clinical Activity 
Screen 
Days 
-21 to -
2 
Check-
in 
Intervention Period 
Follow-up 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to clinic 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge from clinic 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, weight, and BMI3 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs4 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination5 
X 
X 
X 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X  
Drug Alcohol/Cotinine 
/history and screen6 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Visit Number 
 
01 
01A 01B 01C 02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
ED = early 
discontinuation/withdrawal 
Time From Start of IV Infusion 
 
Pre EOI 4hr 8hr 24hr 48hr 72hr Wk1 Wk2 Wk2 Wk2 Wk3 Wk4 Wk8 Wk12 Wk16 Wk20 Wk24 
 
Day of Study1 
D-1 
D1 
D1 D1 D1 D2 D3 D4 D7 D8 D102 D14 D21 D28 D56 D84 D112 D140 
D168 
 
Clinical Activity 
Screen 
Days 
-21 to -
2 
Check-
in 
Intervention Period 
Follow-up 
 
Past and Current 
medical conditions 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study product 
administration7 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NRS 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG8 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
 
 
X 
 
Clinical laboratory6 
X 
X 
 
 
 
 
 
X 
X 
 
X 
 
 
X 
 
X 
X 
Urinalysis6 
X 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
Pregnancy test:(serum) 
(POCBP only)9 
X 
X 
 
 
 
 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
FSH10 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV and hepatitis B and 
C6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Visit Number 
 
01 
01A 01B 01C 02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
ED = early 
discontinuation/withdrawal 
Time From Start of IV Infusion 
 
Pre EOI 4hr 8hr 24hr 48hr 72hr Wk1 Wk2 Wk2 Wk2 Wk3 Wk4 Wk8 Wk12 Wk16 Wk20 Wk24 
 
Day of Study1 
D-1 
D1 
D1 D1 D1 D2 D3 D4 D7 D8 D102 D14 D21 D28 D56 D84 D112 D140 
D168 
 
Clinical Activity 
Screen 
Days 
-21 to -
2 
Check-
in 
Intervention Period 
Follow-up 
 
Test for SARS-CoV-211 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Timed PK sample12 
 
 
X 
X 
X 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Recording of 
AEs/SAEs13 
 
 
 
 
X 
Concomitant medication 
review 
 
 
 
X 
AE = adverse event; BMI = body mass index; COVID‑19 = coronavirus disease; EOI = end of infusion; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; IV-
intravenous; NRS = Numeric Rating Scale; PK = pharmacokinetic(s); POCBP = participant of childbearing potential; SAE = serious adverse event; SARS-CoV-2 = severe acute 
respiratory syndrome-related coronavirus-2 
Visit windows: Schedule Visits 01 through 15 with respect to Day 1. Visit 01 (-10 minutes for PK sample collection and vitals; -1 hour for ECG), Visit 01A (window for start of infusion 
+10 minutes); Visits 01B and 01C (±10 minutes); Visits 02, 03, 04, 05, 06 (±6 hours), Visit 07 (±12 hours); Visits 08, 09, 10 (±2 days), and Visits 11, 12, 13, 14, and 15 (±7 days). 
Assessments should be done as close as possible to nominal time. 
 
1 
Day 1 = day of product administration. Day 1 evaluations prior to product administration will be considered as baseline for assessing subsequent AEs.  
2 
Day 10 outpatient visit is only applicable to 2 sentinel participants. 
3 
Height and weight will be measured and BMI will be calculated at Screening. Only weight will be measured at Check-in and Day 1 
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4 
Vital signs will include body temperature, systolic and diastolic blood pressure, respiratory rate, and pulse. On Day 1, the vital signs and SPO2 will be measured at predose, every 
15 minutes from start of infusion for 2 hours, and at 4 hours and 8 hours postdose. For further details, refer to Section 8.1.2 
5 
A full physical examination will be performed at Screening (at minimum, assessment of skin, head, ears, eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular system, 
abdomen, lymph nodes, and musculoskeletal system/extremities). A brief physical examination (at minimum, assessment of skin, lungs, cardiovascular system, and abdomen 
[liver and spleen]) will be performed at Check-in, at Day 1 (pre-dose), at 8 hours, Day 10 (applicable only for 2 sentinel participants) and at ED visit. A brief physical examination 
will also be performed within 30 to 60 minutes of EOI. Interim physical examinations may be performed at the discretion of the investigator, if necessary, to evaluate AEs or clinical 
laboratory abnormalities. 
6 
A complete list of assessments is provided in Section 10.2. 
7 
Study product administration will be performed following predose activities.  
8 
The electrocardiogram (ECG) taken at Screening and on Day 1 before product administration will be a single reading; however, repeat ECGs are allowed at investigator’s 
discretion to confirm the eligibility. Triplicate 12-lead ECGs will be obtained for all postdose time points. For Visit 01A, ECGs will be taken within 30 minutes of EOI.  
9 
At the Day –1 visit, a serum sample will be sent for pregnancy testing. Pregnancy testing will be conducted on POCBP only on serum samples. Refer to Section 8.1.5. 
10 Females with at least 12 months of amenorrhea must have a serum FSH test performed at screening to confirm postmenopausal status.  
11 The clinic will follow their standard procedures and/or local guidelines with respect to COVID‑19 testing at Check-in, during the intervention period, and at any other time points 
during the study, if deemed necessary by the investigator. The Covid test during the screening period should be performed within -7 days of check in. 
12 The PK blood draw “visits” are defined relative to the exact time of the end of infusion. The exact start and end times of product administration and the time of PK blood draw(s) 
will be recorded to ensure accurate PK analysis. 
13 All AEs/SAEs will be collected from the start of study product infusion. Please refer to Section 8.2.1 for study participation related SAEs. 
Notes 
• 
The timing of planned study assessments may change during the course of the study based on emerging data/in-stream data review (e.g., to obtain data closer to the time of 
peak plasma concentrations) to ensure appropriate monitoring. 
• 
Any changes in the timing of time points for any planned study assessments as the result of emerging pharmacokinetic/pharmacodynamic data from this study must be 
documented and approved by the relevant study team member and then archived in the sponsor and site study files but will not constitute a protocol amendment. 
• 
The Competent Authority (CA) and ethics committee (EC) will be informed of any safety issues that constitute a substantial amendment and require alteration of the safety 
monitoring scheme or amendment of the informed consent form (ICF). The changes will be approved by the CA and the EC before implementation. 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
1.7. 
Schedule of Activities (SoA) Part 3 
Visit Number 
 
01 
01A 01B 01C 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
ED = early 
discontinuation/withdrawal 
Time From Start of SC Infusion 
 
Pre EOI 4hr 
8hr 24hr 48hr 72hr Wk1 Wk2 Wk3 Wk4 Wk8 Wk12 Wk16 Wk20 Wk24 
 
Day of Study1 
D-1 
D1 
D1 
D1 
D1 
D2 
D3 
D4 
D7 D14 D21 D28 D56 D84 D112 D140 
D168 
 
Clinical Activity 
Screen 
Days 
-21 to -2 
Check-
in 
Intervention Period 
Follow-up 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to clinic 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge from clinic 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, weight, and BMI2 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs3 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination4 
X 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X  
Drug Alcohol/Cotinine /history 
and screen5 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Visit Number 
 
01 
01A 01B 01C 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
ED = early 
discontinuation/withdrawal 
Time From Start of SC Infusion 
 
Pre EOI 4hr 
8hr 24hr 48hr 72hr Wk1 Wk2 Wk3 Wk4 Wk8 Wk12 Wk16 Wk20 Wk24 
 
Day of Study1 
D-1 
D1 
D1 
D1 
D1 
D2 
D3 
D4 
D7 D14 D21 D28 D56 D84 D112 D140 
D168 
 
Clinical Activity 
Screen 
Days 
-21 to -2 
Check-
in 
Intervention Period 
Follow-up 
 
Past and Current medical 
conditions 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study product administration6 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PIN and NRS7 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
12-lead ECG8 
X 
 
X 
 
X 
 
X 
X 
X 
X 
 
 
X 
 
 
 
 
X 
 
Clinical laboratory5 
X 
X 
 
 
 
 
X 
X 
X 
X 
X 
 
X 
 
 
X 
 
X 
X 
Urinalysis5 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Pregnancy test:(serum) 
(POCBP only)9 
X 
X 
 
 
 
 
X 
 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
FSH10 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV and hepatitis B and C5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test for SARS-CoV-211 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Visit Number 
 
01 
01A 01B 01C 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
ED = early 
discontinuation/withdrawal 
Time From Start of SC Infusion 
 
Pre EOI 4hr 
8hr 24hr 48hr 72hr Wk1 Wk2 Wk3 Wk4 Wk8 Wk12 Wk16 Wk20 Wk24 
 
Day of Study1 
D-1 
D1 
D1 
D1 
D1 
D2 
D3 
D4 
D7 D14 D21 D28 D56 D84 D112 D140 
D168 
 
Clinical Activity 
Screen 
Days 
-21 to -2 
Check-
in 
Intervention Period 
Follow-up 
 
Timed PK sample12 
 
 
X 
X13 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Recording of injection site 
reactions in 14 days diary 
card14 
 
 
 
 
 
 
 
 
 
 
 
 
Recording of AEs/SAEs15 
 
 
 
 
X 
Concomitant medication 
review 
 
 
 
X 
AE = adverse event; BMI = body mass index; COVID‑19 = coronavirus disease; EOI = end of infusion; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus-1; ISR 
= injection site reaction; NRS = Numeric Rating Scale; PIN = Perception of Injection PK = pharmacokinetic(s); POCBP = participant of childbearing potential; SAE = serious adverse 
event; SARS-CoV-2 = severe acute respiratory syndrome-related coronavirus-2; SC = subcutaneous; SOI = start of infusion 
Visit windows: Schedule Visits 01 through 13 with respect to Day 1. Visit 01 (-10 minutes for PK sample collection and vitals; -1 hour for ECG), Visit 01A (+10 minutes); Visits 01B and 
01C (±10 minutes); Visits 02, 03, and 04 (±6 hours); Visits 05, 06, 07, and 08 (±2 days), and Visits 09, 10, 11, 12, and 13 (±7 days). Assessments should be done as close as possible 
to nominal time. 
 
1 
Day 1 = day of product administration. Day 1 evaluations prior to product administration will be considered as baseline for assessing subsequent AEs. 
2 
 Height and weight will be measured and BMI will be calculated at Screening. Only weight will be measured at Check-in and Day 1. 
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3 
Vital signs will include body temperature, systolic and diastolic blood pressure, respiratory rate, and pulse. on Day 1, the vital signs and SPO2 will be measured at pre-dose and at 
4 hours and 8 hours postdose. For further details, refer to Section 8.1.2. 
4 
A full physical examination will be performed at Screening (at minimum, assessment of skin, head, ears, eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular system, 
abdomen, lymph nodes, and musculoskeletal system/extremities). A brief physical examination (at minimum, assessment of skin, lungs, cardiovascular system, and abdomen 
[liver and spleen]) will be performed at Check-in, at Day 1 (predose), at 8 hours, and at ED visit. Interim physical examinations may be performed at the discretion of the 
investigator, if necessary, to evaluate AEs or clinical laboratory abnormalities. 
5 
A complete list of assessments is provided in Section 10.2. 
6 
Study product administration will be performed following predose activities  
7 
NRS will be administered on Day 1 at the end of the infusion. Additionally, PIN and NRS will be administered on Day 2 and Day 7. 
8 
The electrocardiogram (ECG) taken at Screening and on Day 1 before product administration will be a single reading; however, repeat ECGs are allowed at investigator’s 
discretion to confirm the eligibility. Triplicate 12-lead ECGs will be obtained for all postdose time points.  
9 
At the Day –1 visit, a serum sample will be sent for pregnancy testing. Pregnancy testing will be conducted on POCBP only on serum samples. Refer to Section 8.1.5. 
10 Females with at least 12 months of amenorrhea must have a serum FSH test performed at screening to confirm postmenopausal status.  
11 The clinic will follow their standard procedures and/or local guidelines with respect to COVID‑19 testing at Check-in and during the intervention period, and any other time points 
during the study, if deemed necessary by the investigator. The Covid test during the screening period should be performed within -7 days of check-in. 
12 The PK blood draw “visits” are defined relative to the exact time of the end of infusion. The exact start and end times of product administration and the time of PK blood draw(s) 
will be recorded to ensure accurate PK analysis. All participants will be observed for 4 hours after product administration. Plasma samples of approximately 2 mL will also be 
collected for rHuPH20 analysis at predose, 1 and 4 hours after the end of infusion. 
13 PK blood samples will be collected at end of infusion for GSK3810109 PK analysis and at 1 hour after end of infusion for rHuPH20 analysis. 
14 An ISR that is considered Grade 3 or greater may be referred for dermatology consult and workup (dermatology referral for Grade 3 erythema without other local symptoms will be 
at the discretion of the investigator). Please refer to Section 8.2.7.1 for further details. 
15 All AEs/SAEs will be collected from the start of study product infusion. Please refer to Section 8.2.1 for study participation related SAEs. 
 
Notes 
• 
The timing of planned study assessments may change during the course of the study based on emerging data/in-stream data review (e.g., to obtain data closer to the time of 
peak plasma concentrations) to ensure appropriate monitoring. 
• 
Any changes in the timing of time points for any planned study assessments as the result of emerging pharmacokinetic/pharmacodynamic data from this study must be 
documented and approved by the relevant study team member and then archived in the sponsor and site study files but will not constitute a protocol amendment. 
The Competent Authority (CA) and ethics committee (EC) will be informed of any safety issues that constitute a substantial amendment and require alteration of the safety monitoring 
scheme or amendment of the informed consent form (ICF). The changes will be approved by the CA and the EC before implementation

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2. 
INTRODUCTION 
Despite significant progress in the treatment and prevention of human immunodeficiency 
virus (HIV) infection, HIV/(acquired immunodeficiency syndrome) AIDS has remained a 
major global public health problem since the discovery of the virus in 1983. Reports by 
the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimate that 79.3 million 
people have been infected with HIV since the start of the epidemic, contributing to 
36.3 million deaths from AIDS-related illnesses [UNAIDS, 2021]. Despite these 
statistics, global incidences of new HIV infections have actually declined from peak rates 
in the mid-1990s; a reduction attributed in part to increased availability of antiretroviral 
therapy (ART) and the effective execution of prevention/treatment programs such as 
those that target mother-to-child transmission. Unfortunately, HIV infection is extremely 
complex and none of the current therapeutic regimens can cure an infection or induce a 
full recovery of the host immune system. Long-term toxicities, emergent and transmitted 
drug resistance, and drug-drug interactions create a continued unmet medical need for 
new antiretroviral medications (with new modes of action). Current approved treatment 
therapies require daily therapy. Thus, novel therapeutic strategies are being investigated. 
The Vaccine Research Centre (VRC)/National Institute of Allergy and Infectious 
Diseases is investigating clinical applications of broadly neutralizing human monoclonal 
antibodies (bNAbs) that bind the HIV type 1 (HIV-1) envelope protein [Huang, 2016; 
Huang, 2012;  
Kwon, 2012; Wu, 2010]. Such antibodies block infection of target cells in vitro and have 
been shown to prevent infection of non-human primates in in vivo models for HIV 
[Mascola, 2000; Pegu, 2014; Rudicell, 2014]. Through advances in B-cell immunology 
utilizing single-cell cloning methods, next-generation sequencing, high throughput 
computational analysis techniques, and increased cell culture survivability procedures, an 
extensive group of HIV-1 bNAbs have been isolated. These include an HIV-1 specific 
bNAb identified as N6 that was recently isolated from a patient with a 21-year known 
history of HIV-1 infection that was controlled in the absence of ART [Huang, 2016]. 
In order to improve the pharmacokinetics (PK) of N6, 2 amino acid substitutions 
(methionine to leucine and an asparagine to serine M428L/N434S, that collectively 
yielded N6LS [GSK3810109]) were introduced within the C-terminus of the heavy chain 
constant region of N6 via site-directed mutagenesis to increase its binding affinity for the 
neonatal Fc-receptor (FcRn). This modification results in enhanced recirculation and 
longer plasma half-life of GSK3810109 relative to the wild-type Ab. 
GSK3810109 is being developed for the prevention of HIV-1 infection in uninfected 
adults and for treatment of HIV-1 infection in infected adults. The first-time-in-human 
(FTIH) study (VRC 609) is currently ongoing to evaluate the safety, tolerability, and PK 
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2.1. 
Study Rationale 
GSK3810109 (identified as N6LS and VRC-HIVMAB091-00-AB in scientific reports), 
is a highly potent and broadly neutralizing monoclonal antibody directed against the 
CD4-binding site of the HIV-1 envelope glycoprotein 120 subunit (gp120). GSK3810109 
can mediate extraordinary breadth and potency against various HIV isolates, including 
strains traditionally resistant to other antibodies in this class.  
This study is designed to evaluate safety, tolerability, and PK endpoints in healthy adult 
participants, when GSK3810109 is administered as either subcutaneous (SC) injection 
(Part 1 and Part 3 of study) or by intravenous (IV) infusion (Part 2 of study). Dosing by 
either SC or IV infusion may each offer practical advantages related to tolerability, 
simplicity, or frequency of dosing in the administration of GSK3810109. The inclusion of 
both routes of administration in this study is an efficient design to enable rapid 
progression to future studies using either 1 or both routes of administration.  
This current study is aimed at investigating options that may reduce the frequency of 
administration and thus the burden on patients by evaluating the feasibility of a high dose 
of GSK3810109 administered IV, and larger SC dose volumes (>2.5 mL) of 
GSK3810109 using a 20 mg/kg or 
 
In this study, an IV dose of 60 mg/kg of GSK3810109 will be administered, which may 
offer the potential for an ultra-long-acting target profile to support administration every 4 
to 6 months, thus improving adherence. Medication adherence and decreasing frequency 
of clinic visits is the most important determinant for sustained viral suppression and 
long-term treatment success. 
The rHuPH20 enzyme facilitates the SC delivery of co‐administered therapeutics. 
Hyaluronidase injection is effective for the use as an adjunct to increase the absorption 
and dispersion of other injected drugs; for hypodermoclysis; as an adjunct in SC 
urography for improving the resorption of radiopaque agents (United States Federal 
Register [23 September 1970]). 
 
The FTIH Protocol VRC 609 study is currently ongoing to evaluate the safety, 
tolerability, and PK of GSK3810109 (N6LS). As of 4 August 2021, no significant safety 
findings were noted. Two Grade 3 events of injection site erythema, one after receiving 
5 mg/kg SC N6LS + 2000 U rHuPH20/mL and one after receiving 20 mg/kg SC N6LS + 
2000 U rHuPH20/mL, were noted; however, the Grade 3 erythema observed in both 
individuals was well tolerated and judged to not represent an increased safety risk for 
study participants. 
 
CCI

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2.2. 
Background 
2.2.1. 
GSK3810109 
GSK3810109 belongs to a class of broadly neutralizing HIV antibodies. These antibodies 
target the CD4-binding site of the HIV envelope protein. 
Protocol VRC 609, the FTIH study of GSK3810109 (N6LS) in healthy individuals 
assesses the safety, tolerability, and PK of this antibody. The FTIH study is an 
open-label, single- and repeat-dose administration of GSK3810109 (N6LS) given across 
6 dose groups of either a single IV infusion at 5, 20, or 40 mg/kg dose levels (N=3 for 
each group), a single SC injection at the 5 mg/kg dose level (N=4), in 3 administrations 
12 weeks apart by SC injection at the 5 mg/kg dose level (N= 5) or in 3 administrations 
12 weeks apart by IV infusion at the 20 mg/kg dose level (N=5). Thus, in total, 23 
participants were enrolled and 22 participants completed the study as of 04 Aug 2021. 
One participant was terminated from the study after enrolling but prior to product 
administration. The VRC 609 study is now being conducted to evaluate a single 
5 or 20 mg/kg dose of GSK3810109 (N6LS) co-mixed with rHuPH20 by SC infusion.  
As of 4 August 2021, no significant safety findings were noted. GSK3810109 was 
generally well-tolerated, with no serious adverse events (SAEs), dose-limiting toxicities, 
or deaths reported.  
All unsolicited events were mild or moderate in severity except for one Grade 3 diarrhea 
that began 4 days after administration, spontaneously resolved 2 days later, and was 
determined to be possibly related to GSK3810109 (N6LS). Solicited systemic symptoms 
were reported in 4/14 (29%) participants following IV administration and 3/12 (25%) 
participants following SC administration. Symptoms reported after IV administration 
included 4 events of mild headache, 1 mild event each of malaise, chills, and nausea. 
Symptoms reported after SC administration included 1 mild event each of malaise, 
myalgia, headache, and nausea. No fever occurred after IV or SC administration. 
Solicited local symptoms reported included moderate bruising (1/14 participants, 7%) 
following IV administration. Solicited local symptoms after SC administration included 
mild pain/tenderness (9/12 participants, 75%), mild to moderate swelling 
(4/12 participants, 33%), mild to severe redness (6/12 participants, 50%), and mild 
pruritus (3/12 participants, 25%).  
A study pause occurred on 23 July 2021 after criteria for a pause was met due to two 
Grade 3 injection site erythema events not resolving during the solicited diary card 
reporting period. A participant after receiving 5 mg/kg SC N6LS + 2000 U rHuPH20/mL 
developed injection site erythema to a maximum diameter of 13 cm, which resolved after 
30 days. Another participant after receiving 20 mg/kg SC N6LS + 2000 U rHuPH20/mL 
developed injection site erythema to a maximum of 20 cm, which resolved after 7 days. 
Since the episodes of Grade 3 erythema observed in both individuals were well tolerated, 
not accompanied by any other symptoms or laboratory abnormalities that would indicate 
potential systemic toxicity, and resolved without clinical sequelae, the erythema was 
judged to not represent an increased safety risk for study participants. Therefore, the 
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(PSRT) determined that the protocol would not need to be paused for future events of the 
same type and severity.  
There is known data for GSK3810109 along with experiences from other CD4-binding 
site bNAbs VRC01 [Lynch, 2015] and 3BNC117 [Caskey, 2015] as well as the modified 
versions of VRC01LS and VRC07-523LS, which are designed for extended serum 
half-life by increased binding affinity to the FcRn, which are similar to GSK3810109 
[Gaudinski, 2018] [Gaudinski, 2019]. 
These other bNAbs were administered at similar doses, frequency and routes as 
GSK3810109 in the FTIH VRC 609 study and have been generally well-tolerated with no 
deaths or SAEs assessed as related to the investigational drug. The predominant local 
reactogenicity complaint has been mild pain/tenderness, although reports of mild 
injection site pruritus, redness, and swelling have occurred at modestly higher 
frequencies with the SC administration. Malaise, muscle pain, and headache have been 
the most frequently reported events noted in the 3 days post product administration. 
These events have been mild in severity and transient. Although infrequent, infusion 
reactions comprised of chills, rigors, myalgia, and headache have been reported after IV 
infusions at product doses of 10 to 40 mg/kg. These reactions have been transient, 
resolving within 24 hours of onset, without sequelae, and have generally been treated 
with over-the-counter analgesics and antipyretics. 
A detailed description of the chemistry, pharmacology, and safety of GSK3810109 is 
provided in the current IB [Investigator’s Brochure]. 
2.2.2. 
Recombinant Human Hyaluronidase PH20 (rHuPH20) 
The rHuPH20 enzyme facilitates the SC delivery of co‐administered therapeutics by 
depolymerizing hyaluronan (HA) in the extracellular matrix of the SC tissue that 
normally serves to restrict bulk fluid flow. Enhanze™ Drug Product (EDP) is an 
investigational ready to use injectable drug product that contains 1 mg/mL 
(110,000 U/mL) rHuPH20. The rHuPH20 is the active ingredient of the commercial 
product Hylenex® recombinant (hyaluronidase human injection), which has been Food 
and Drug Administration (FDA)-approved since 2005 for SC fluid administration for 
achieving hydration, to increase the dispersion and absorption of other injected drugs, and 
in SC urography for improving resorption of radiopaque agents. High dose biologics 
previously limited to the IV route of administration due to volume, can be successfully 
administered SC with rHuPH20. 
rHuPH20 co-administration can provide additional benefits, such as improved absorption, 
increased bioavailability, and reduced PK variability of certain agents [Morrow, 2011; 
Morcos, 2013]. Importantly, the local permeability barrier tissue changes induced by 
rHuPH20 are reversible within 24 to 48 hours after administration, without any 
inflammatory or histological changes [Locke, 2019].  
As of 02 December 2021, 1,592 participants were exposed to Hylenex and other 
rHuPH20 drug products in 30 clinical studies conducted under IND 66,888 or in 

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post-marketing Phase 4 studies. Individual doses of rHuPH20 ranged from 15 to 
96,000 U (see the current IB; [Investigator’s Brochure rHuPH20]). 
Across all Halozyme-sponsored studies, SC injections of rHuPH20 have been 
well-tolerated in healthy participants, dehydrated pediatric participants, hospice and 
palliative care participants, participants with type 1 and 2 diabetes, and participants with 
rheumatoid arthritis. The SC injections of rHuPH20 alone or in combination with 
hydration fluids (Lactated Ringer’s, normal saline), co-injected small molecules 
(morphine, ceftriaxone, ondansetron), peptides (insulin, and insulin analogs), and proteins 
(IgG and adalimumab) have been well-tolerated in all clinical trials [Locke, 2019; 
Shpilberg, 2013]. Most adverse events (AEs) were mild, transient injection site reactions 
(ISRs), including erythema, pain, bruising, pruritus, burning, tenderness, edema, 
induration, irritation, paresthesia, numbness, and rash. Moderate ISRs, which have 
occurred less frequently, include burning, erythema, pain, and numbness. 
Mild-to-moderate headache was also commonly reported. 
rHuPH20 is currently co-formulated with 4 approved anticancer therapies, trastuzumab 
(Herceptin Hylecta™/Herceptin® SC), pertuzumab/trastuzumab (Phesgo™), daratumumab 
(Darzalex Faspro™), rituximab (i.e., Rituxan Hycela®/Rituxan® SC/Mabthera® SC), and 
dosed sequentially with human immunoglobin to treat primary immunodeficiency 
(HyQvia®/HYQVIA®). 
The specific non-clinical pharmacology, PK, and toxicity studies evaluating rHuPH20 are 
summarized in the rHuPH20 current IB, Section 4 [Investigator’s Brochure rHuPH20]. 
2.3. 
Benefit/Risk Assessment 
2.3.1. 
Risk Assessment 
2.3.1.1. 
Risks of GSK3810109 and MAb Administration 
Typically, the side effects of monoclonal antibodies (MAbs) are mild but may include 
reactions at injection site (pain, redness, bruising, swelling), fever, chills, rigors, nausea, 
vomiting, pain, headache, dizziness, shortness of breath, bronchospasm, hypotension, 
hypertension, pruritus, rash, urticaria, angioedema, diarrhea, tachycardia, or chest pain. 
Up to Grade 3 injection site erythema has been observed after GSK3810109 + rHuPH20 
injection, and some ISRs have lasted up to 6 weeks before completely resolving. Clinical 
use of MAbs that are targeted to cytokines or antigens associated with human cells may 
be associated with an increased risk of infections (Hansel, 2010); however, this is not 
expected to be a risk for a MAb targeted to a viral antigen. 
Administration of MAbs may cause immune reactions such as acute anaphylaxis, 
cytokine release syndrome, serum sickness and the generation of antibodies. However, 
these reactions are rare and more often associated with MAb targeted to human proteins 
or with the use of murine or chimeric MAbs which would have a risk of human anti-
mouse antibodies (Hansel, 2010). In this regard, as GSK3810109 is expected to have a 
low risk of such side effects since it is directed against a viral antigen and is human in 
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Published experience with other human MAbs directed against the cell surface targets on 
lymphocytes have shown that infusion of an MAb may be associated with cytokine 
release, causing a reaction known as “cytokine release syndrome” (CRS) (Bugelski, 
2009). Most infusion-related events occur within the first 24 hours after beginning 
administration. Severe reactions, such as anaphylaxis, angioedema, bronchospasm, 
hypotension, and hypoxia, are infrequent and more often associated with MAbs targeted 
to human proteins or when a non-human MAb, such as a murine MAb, is used (Hansel, 
2010). Specifically, with regard to the rare CRS reactions, these generally occur within 
the first few hours of beginning the infusion and are more common with the first MAb 
infusion received. This is because the cytokine release is associated with lysis of the cells 
targeted by the MAb and the burden of target cells is greatest at the time of the first MAb 
treatment. With licensed therapeutic MAbs, CRS is managed by temporarily stopping the 
infusion, administration of histamine blockers and restarting the infusion at a slower rate 
(Vogel, 2010). 
Delayed allergic reactions to other MAbs may include a serum sickness type of reaction, 
which is characterized by urticaria, fever, lymph node enlargement, and joint pains. 
These symptoms may not appear until several days after the exposure to the MAb and is 
noted to be more common with chimeric types of MAbs (Hansel, 2010). 
There are several FDA-licensed MAbs for which reactions related to the rate of IV 
infusion have been described. Some symptoms may be treated by slowing or stopping the 
infusion. Supportive treatment or pre-medications may also be indicated for some signs 
and symptoms.   
Other bNAbs under development for the treatment of HIV-1 that operate through the 
same mechanism of action as GSK3810109 (CD4 binding site) include VRC01, 
VRC01LS (Gaudinski, 2018) and 3BNC117. These bNAbs were well tolerated in clinical 
studies without clear adverse safety concerns. The predominant local reactogenicity 
complaint was mild pain/tenderness, although reports of mild injection site pruritus, 
redness, and swelling occurred at modestly higher frequencies with SC administration. 
Malaise, muscle pain, and headache were the most frequently reported solicited 
complaints noted in the 3 days post product administration. These events have been 
mostly mild in severity and transient. Infrequent, urticaria and infusion reactions 
comprising of chills, rigors, myalgia, headache, and/or fever have been reported after IV 
infusions. Participation in this study may limit a participant’s eligibility for other future 
MAb studies. 
2.3.1.2. 
Risks of EDP Co-administration  
Co-administration of EDP (high concentration rHuPH20) may cause mild, transient ISRs, 
including erythema, pain, bruising, pruritus, burning, tenderness, edema, induration, 
irritation, paresthesia, numbness, and rash. Moderate ISRs have occurred less frequently 
and include burning, erythema, pain, and numbness. Mild to moderate headache is also 
commonly reported. AEs in clinical trials have otherwise reflected the adverse reaction 
profiles of the co-administered drug or have been associated with the rapid introduction 
of a relatively large volume of fluid in the SC tissue. 

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2.3.1.3. 
Risks of Blood Drawing 
Blood drawing may cause pain and bruising and may, infrequently, cause a feeling of 
lightheadedness or fainting. Rarely, it may cause infection at the site where the blood is 
taken. In this study, an IV line that can be used for the collection of blood may be left in 
place for several hours on the days when there are frequent PK blood draws. Problems 
from use of an IV line for blood drawing are generally mild and may include pain, 
bruising, minor swelling or bleeding at the IV site and rarely, infection, vein irritation 
(called phlebitis), or blood clot. 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Investigational Product (IP) GSK3810109 
Serious/severe immune 
reactions 
Anaphylaxis and CRS  
Non-clinical 
No serious/severe immune reactions noted in the 
non-clinical rat study. 
Clinical 
Administration of MAbs may cause immune reactions such 
as acute anaphylaxis (anaphylaxis is a life-threatening 
reaction with respiratory, cardiovascular, cutaneous, or 
gastrointestinal manifestations), serum sickness and the 
generation of antibodies. However, these reactions are rare 
and more often associated with MAbs targeted to human 
proteins or with the use of murine MAbs, which would have 
a risk of human anti-mouse antibodies.  
Cytokine release syndrome reactions most commonly occur 
within the first few hours of beginning the infusion and are 
more common with the first MAb infusion received. This is 
because cytokine release is associated with lysis of cells 
targeted by the MAb and the burden of target cells is 
greatest at the time of the first MAb. 
GSK3810109 is expected to have a low risk for 
serious/severe immune reactions as it is directed against a 
viral antigen and is human in sequence origin. No 
Vital signs will be monitored and prompt treatment of 
anaphylaxis is critical, with SC or intramuscular 
epinephrine and IV fluids. Adjunctive measures 
include airway protection, antihistamines, steroids, 
and beta agonists. Some symptoms may be treated 
by slowing or stopping the infusion. Supportive 
treatment may also be indicated for some signs and 
symptoms. 
Patients with anaphylaxis should be closely 
monitored for the possibility of recurrent symptoms 
after initial resolution. 
Urinary and serum histamine levels and plasma 
tryptase levels drawn after onset of symptoms may 
assist in diagnosis. 

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serious/severe immune reactions have been previously 
observed with GSK3810109. 
Local reactogenicity (ISRs) 
Non-clinical 
The repeat dose IV and SC administration of GSK3810109 
at 40 and 400 mg/kg IV and 5 and 50 mg/kg SC in male and 
female Sprague Dawley rats produced test article-related 
effects in injection site irritation (slight erythema observed 
with low incidence, reversible, considered not toxicologically 
relevant). 
Clinical 
In Study VRC 609 as of 04 August 2021, solicited local 
symptoms reported included moderate bruising 
(1/14 participants, 7%) following IV administration. Solicited 
local symptoms after SC administration included mild 
pain/tenderness (9/12 participants, 75%), mild to moderate 
swelling (4/12 participants, 33%), mild to severe redness 
6/12 participants, 50%), and mild pruritus (3/12 participants, 
25%). 
Exclusion criteria as described in Section 5.2 will 
prohibit participants with an underlying skin disease 
or disorder (i.e., infection, inflammation, dermatitis, 
eczema, drug rash, drug allergy, psoriasis, food 
allergy, urticaria), or tattoos that would interfere with 
assessment of injection sites. 
Participants will be closely monitored for 
local/systemic reactions.  
Administration advice to minimize risk of poor 
administration technique giving rise to ISRs. Advice 
on care, monitoring, natural course, and treatment of 
ISRs given in study documentation. 
Advice to participants on care of injection site on 
day/days immediately post administration, use of 
analgesia, compresses where appropriate. 
Participants will be closely monitored for ISRs 
particularly for signs of pain, tenderness, infections, 
erythema, swelling, induration, or nodules 
(granulomas or cysts) throughout the study.  

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Complications of ISRs such as infections (abscess, 
cellulitis) and collections of fluid requiring drainage 
will be monitored.  
Significant ISRs will be photographed and referred to 
a dermatologist for specialist advice and possible 
biopsy. 
Systemic reactogenicity 
Non-clinical 
In the repeat-dose study in Sprague Dawley rats of 3 weeks’ 
duration, 2 females given 40 mg/kg/IV showed hypoactivity 
and prostrate posture on Day 21 immediately and/or 2 to 4 
hours post dose with recovery within 24 hours, consistent 
with an infusion-related reaction. 
Clinical 
The solicited systemic symptoms were reported in 
4/14 (29%) participants following IV administration and 3/12 
(25%) participants following SC administration. Symptoms 
reported after IV administration included 4 events of mild 
headache, 1 mild event each of malaise, chills, and nausea. 
Symptoms reported after SC administration included 1 mild 
event each of malaise, myalgia, headache, and nausea. No 
Participants will be closely monitored for local 
(appearance of symptoms)/systemic reactions. 
IV access will be placed in an arm vein in an aseptic 
manner. GSK3810109 will be diluted with normal 
saline to infuse approximately 250 mL of solution at 
the appropriate concentration over approximately 60 
minutes but not to exceed 2 hours. If the participant 
experiences side effects during the infusion, the rate 
of infusion may be slowed or stopped to alleviate the 
symptoms.  
 Supportive treatment or pre-medications may be 
indicated for some signs and symptoms. 
Vital signs and SPO2 will be monitored during IV 
infusions 

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fever occurred after IV or SC administration. 
All reported instances of systemic reactogenicity (malaise, 
myalgia, headache, nausea, chills) were mild (Grade 1) and 
were reported as recovered within 1 day of onset.  
Gastrointestinal disorders 
(Diarrhea) 
Non-clinical 
Not applicable 
Clinical 
In the Phase 1 study, 3 participants experienced diarrhea 
(Grade 1 to Grade 3) considered related by the investigator. 
Time to onset was 1 to 6 days from last dose and all 
recovered within 2 days. One additional participant with 
Grade 1 diarrhea was not considered related (time to onset 
was 19 days post dose). 
Careful monitoring of gastrointestinal AEs will occur 
throughout the study. Serious/severe events will be 
managed appropriately and will be followed to 
resolution as per standard ViiV Medical Monitoring 
practices. 
Liver chemistry elevations  
Non-clinical 
The repeat-dose IV and SC administration of GSK3810109 
at 40 and 400 mg/kg IV and 5 and 50 mg/kg SC in Sprague 
Dawley rats produced test article-related effects in clinical 
chemistry with up to 1.5-fold increase in AST, ALT and/or 
ALP, correlating with the histopathologic findings in the liver, 
within high-end of normal ranges and considered not to 
Participants with liver impairment based on screening 
liver chemistry will be excluded: 
Participants with ALT> × 1.5 ULN or total bilirubin 
>1.5 × ULN are excluded (Exclusion criteria #16 and 
#17). 
Liver aminotransferases (ALT and AST) will be 
monitored throughout this study (refer to SoA, 

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have reached a level of toxicity. 
Clinical 
A total of 3 (14%) participants experienced transient 
Grade 1 or 2 liver enzyme elevations (2 ALT elevation; 
1 AST elevation). 
Section1.5, Section 1.6, and Section 1.7) and the 
liver chemistry stopping criteria will be adopted as 
described in Section 10.5 of this protocol.  
 Liver chemistry stopping criteria:  
• ALT≥3 × ULN 
• If ALT≥3 × ULN AND bilirubin 2 × ULN (>35% 
direct bilirubin) or INR >1.5, i.e., Hy’s case, report 
event as an SAE. 
Neutropenia 
Non-clinical 
The repeat-dose IV and SC administration of GSK3810109 
at 40 and 400 mg/kg (IV) and 5 and 50 mg/kg (SC) in 
Sprague Dawley rats produced test article-related effects in 
monocytes up to 2.6-fold increase, reticulocytes up to 3.7-
fold increase, and eosinophils up to 72.7% decrease, all 
reversible, correlated with non-adverse histopathology 
findings in axillary lymph nodes, spleen and bone marrow 
and/or organ weight findings in spleen. 
Clinical 
A Grade 2 neutropenia in 1/22 participant was considered 
possibly related by the investigator in the Phase 1 study. 
Baseline neutrophil count was 3.15 × 103 cells/L. 
Close monitoring of blood counts in participants 
initiating therapy will be conducted throughout this 
study (refer to SoA, Section 1.5, Section 1.6, and 
Section 1.7). 

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Neutropenia (0.75 × 103 cells/L) started 23 days post dose 
(single IV dose; 20 mg/kg) and returned to 
3.11 × 103 cells/L (within normal range) 13 days later at 
the next specimen collection. No intercurrent illness or 
confounding concomitant medication was reported. 
Immunogenicity 
Non-clinical 
GSK3810109 exhibited lower serum concentrations after 
repeat administration via both routes in the dose ranges 
studied suggesting the formation of 
 which was more 
prominent in the SC dose groups but also apparent in the 40 
mg/kg IV dose group. Following repeated administration of 
400 mg/kg IV during the main study, there was faster 
clearance in some animals by Day 56. In addition, 2 females 
given 40 mg/kg/IV showed hypoactivity and prostrate 
posture on Day 21 immediately and/or 2 to 4 hours post 
dose with recovery within 24 hours, consistent with an 
infusion-related reaction. The toxicities observed are 
therefore considered possibly to be a result of the formation 
and subsequent clearance of 
 although this cannot be 
confirmed since immunogenicity analysis was not 
conducted. 
Clinical 
Animal studies are generally not predictive of 
immunogenicity and sequelae related to immunogenicity in 
The emergence of 
 will be actively monitored 
using a validated 
 (screening, 
confirmation, and titration). 
CCI
CCI
CCI
CCI

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humans. There were 
 detected in 2/22 (9%) of 
GSK3810109-treated participants at any time after dosing, 
however, no neutralizing activity was exhibited. There were 
no discernible effects of immunogenicity on the safety and 
PK profiles from the Phase 1 study. 
 AE = adverse event; ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CRS = cytokine release syndrome; 
INR = international normalized ratio; ISR = injection site reaction; IV = intravenous; MAb = monoclonal antibody; PK = pharmacokinetic(s); SAE = serious adverse event; SC = 
subcutaneous; SoA = schedule of activities; ULN = upper limit of normal. 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Recombinant Human Hyaluronidase PH20 (rHuPH20) 
Spread of localized infection 
rHuPH20 should not be injected into or around an 
infected or acutely inflamed area because of the 
danger of spreading a localized infection. 
Training will be provided to relevant staff regarding 
proper injection technique. 
 
Hypersensitivity 
Hypersensitivity, allergic, and anaphylactic-like 
reactions have been associated with animal-derived 
hyaluronidases but have not been associated with 
rHuPH20. 
Participants with a history of hypersensitivity to 
hyaluronidases are excluded. 
Inadvertent IV administration 
In a study of healthy volunteers administered 10,000 U 
or 
 of rHuPH20 intravenously, rHuPH20 had a 
half-life of less than 10 minutes and was well tolerated. 
There were no associated serious adverse effects 
(Investigator’s Brochure rHuPH20 ). 
Training will be provided to relevant staff regarding 
proper injection technique. 
No mitigation activities are needed if there is suspected 
IV administration of rHuPH20. 
Injection Site Reactions (ISRs) 
rHuPH20 may cause ISRs. These ISRs are mostly 
mild, transient ISRs, including erythema, pain, 
Participants will be closely monitored for throughout the 
study. 
CCI
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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Recombinant Human Hyaluronidase PH20 (rHuPH20) 
(Applicable only for Part 1 and 
Part 3) 
bruising, pruritus, burning, tenderness, edema, 
induration, irritation, paresthesia, numbness, and rash. 
Moderate ISRs occur less frequently, include burning, 
erythema, pain, and numbness (Investigator’s 
Brochure rHuPH20). 
 
rHuPH20 may potentially alter the ISR profile of 
GSK3810109. 
 
Significant ISRs will be photographed and referred to a 
dermatologist for specialist advice and possible biopsy. 
 
Most AEs reported in clinical trials with rHuPH20 were 
mild, transient ISRs, including erythema. It is currently 
unknown if rHuPH20 may impact the ISR profile of 
GSK3810109. 
 
 

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2.3.2. 
Benefit Assessment 
There are no direct benefits to study participants from study participation. Others may 
benefit from knowledge gained in this study that may aid in the development of HIV 
risk-reduction or therapeutic methods. 
2.3.3. 
Overall Benefit: Risk Conclusion 
Given the non-clinical and clinical profile to date, data from other bNAb studies, the 
frequent visit schedule, and the proposed dose levels for SC and IV administration (refer 
to Section 4.3), the overall risk to healthy participants in this study is predicted to be low 
and manageable.

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3. 
OBJECTIVES AND ENDPOINTS AND/OR ESTIMANDS 
Objectives 
Endpoints 
Primary 
 
• To evaluate the safety and tolerability of a 
single dose of GSK3810109 administered 
SC with rHuPH20 or IV in healthy adult 
participants 
Part 1 and Part 3 (SC injection) 
• The number and percentages of 
participants who have AEs (Grade 2 or 
higher) and SAEs following GSK3810109 
SC administration through Week 24 
• The number and percentages of 
participants who have ISRs within 7 days 
following GSK3810109 SC administration 
• The incidence of Grade 2 to 4 elevated 
ALT/AST following GSK3810109 SC 
administration 
Part 2 (IV infusion)  
• The number and percentages of 
participants who have AEs and SAEs 
following GSK3810109 IV administration 
through Week 24 
• The incidence of Grade 2 to 4 elevated 
ALT/AST following GSK3810109 IV 
administration through Week 24 
Secondary 
 
• To evaluate the PK of a single dose of 
GSK3810109 administered SC with 
rHuPH20 or IV in healthy adult participants  
• Assessment of GSK3810109 PK 
parameters including AUC(0-inf), AUC(0-t), 
Cmax, Tmax, and t1/2 (if possible) 
• To assess the severity and acceptance of 
pain and ISRs after SC administration of 
GSK3810109 with rHuPH20 
• Dimension score “acceptance of ISRs” and 
individual item score assessing pain at Day 
2 and Day 7 using the PIN Questionnaire  
• Proportion of participants who are bothered 
or affected by the pain and local reactions 
as a result of the injection as measured by 
the PIN on Days 2 and 7 

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Objectives 
Endpoints 
• Post-injection pain assessment using NRS 
at Days, 1, 2, and 7 
• The incidence and duration of ISRs 
assessed overall and by grade including 
the duration at grade 
• To assess the severity of pain after IV 
administration of GSK3810109 
• Post-infusion pain assessment using NRS 
at Days, 1, 2, and 7 
• To evaluate additional safety parameters 
following administration of GSK3810109 
SC with rHuPH20 or IV in healthy adult 
participants 
• Change from baseline in clinical laboratory 
assessments, ECGs, and vital sign 
measurements 
Exploratory 
 
; AE = adverse event; ALT = alanine aminotransferase; AST = aspartate 
aminotransferase; AUC(0-inf) = area under the plasma concentration-time curve from time zero extrapolated to 
infinity; AUC(0 t) = area under the plasma concentration-time curve from time zero to time of last observed 
quantifiable concentration; Cmax = maximum observed concentration; ECG = electrocardiogram; ISR = injection 
site reaction; IV = intravenous (ly); NRS = Numeric Rating Scale; PIN = Perception of Injection; PK = 
pharmacokinetics; SAE = serious adverse event; SC = subcutaneous (ly); t1/2 = apparent terminal phase 
half-life; Tmax = time of maximum observed concentration 
Primary estimand 
The primary questions of interest are: What is the safety and tolerability of a single 
20 mg/kg SC dose of GSK3810109 co-administered with rHuPH20 or a single 60 mg/kg 
IV dose of GSK3810109 or 
 
? 
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The primary safety estimands are described by the following attributes: 
• Population: Healthy male and female participants aged 18 to 65 years of age, 
inclusive. 
• Treatment conditions:  
• Part 1: Single 20 mg/kg SC dose of GSK3810109 co-administered with rHuPH20. 
•  Part 2: Single 60 mg/kg IV dose of GSK3810109.  
• 
 
• Variables:  
• Part 1 and Part 3: Incidence of AEs (Grade 2 or higher) and SAEs through Week 
24, incidence of ISRs within 7 days of GSK3810109 administration, and 
incidence of Grade 2 to 4 elevated alanine aminotransferase (ALT)/ aspartate 
aminotransferase (AST) values.  
• Part 2: Incidence of AEs and SAEs through Week 24 and incidence of Grade 2 to 
4 elevated ALT/AST values.  
• Summary measures: 
• Part 1 and Part 3: Number and percentage of participants reporting AEs (Grade 2 
or higher) or SAEs through Week 24; number and percentage of participants 
reporting ISRs within 7 days of GSK3810109 administration; number and 
percentage of participants with Grade 2 to 4 elevated ALT/AST.  
• Part 2: Number and percentage of participants reporting AEs or SAEs through 
Week 24; number and percentage of participants with Grade 2 to 4 elevated 
ALT/AST.  
• Intercurrent events (Part 1, Part 2, and Part 3):  
• Discontinuation from study for any reason: Treatment policy strategy will be 
applied to address this intercurrent event, as safety data will be collected at the 
follow-up visit and will be reported for all participants  
• Rationale for Estimands: Interest lies in the safety and tolerability for a participant 
receiving either a single SC dose of GSK3810109 co-administered with rHuPH20 or 
a single IV dose of GSK3810109.  
Secondary estimands 
The secondary PK questions of interest are: What is the PK profile of a single 20 mg/kg 
SC dose of GSK3810109 co-administered with rHuPH20, or a single 60 mg/kg IV dose 
of GSK3810109, or 
 
? 
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These secondary PK estimands are described by the following attributes: 
• Population: Healthy male and female participants aged 18 to 65 years of age, 
inclusive. 
• Treatment conditions: 
• Part 1: Single 20 mg/kg SC dose of GSK3810109 co-administered with rHuPH20. 
•  Part 2: Single 60 mg/kg IV dose of GSK3810109. 
•  
    
• Variables (Part 1, Part 2, and Part 3): 
• Assessment of GSK3810109 PK parameters: AUC(0-inf), AUC(0-t), Cmax, 
Tmax, and t1/2 
• Summary measures (Part 1, Part 2, and Part 3): 
• Summary statistics (arithmetic mean, geometric mean, median, standard 
deviation, minimum, maximum, and coefficient of variation) will be 
summarized. 
• Intercurrent events (Part 1, Part 2, and Part 3): 
• Discontinuation from study for any reason: While-on treatment strategy will be 
applied to address this intercurrent event. (Only on-treatment PK data prior to 
the intercurrent event is of interest for the secondary PK estimands). 
Additional secondary questions of interest are: Part 1: What is the severity and 
acceptance of pain and ISRs after a single 20 mg/kg SC dose of GSK3810109 
co-administered with rHuPH20 in healthy adults? Part 2: What is the severity of pain 
after a single 60 mg/kg IV dose of GSK3810109 in healthy adults? 
 
 
 
These secondary severity and acceptance estimands are described by the following 
attributes: 
• Population: Healthy male and female participants aged 18 to 65 years of age, 
inclusive. 
• Treatment conditions:  
• Part 1: Single 20 mg/kg SC dose of GSK3810109 co-administered with rHuPH20.  
• Part 2: a single 60 mg/kg IV dose of GSK3810109.  
•
  
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• Variables: 
Part 1 and Part 3: 
• Dimension score and individual item score assessing pain at Day 2 and Day 7 
from the Perception of Injection (PIN) Questionnaire; following injection, 
incidence of pain and local reactions where participants reported being bothered 
or affected using the PIN Questionnaire on Day 2 and Day 7; numeric rating 
scale (NRS) pain assessment scores following injection at Days 1, 2 and 7; and 
incidence and duration of ISRs and duration of grade of ISRs. 
Part 2: 
• Numeric rating scale (NRS) pain assessment scores following infusion, at Days 1, 
2 and 7.  
• Summary measures: 
Part 1 and Part 3: 
• Summary statistics for dimension score “acceptance of ISRs” and individual item 
score assessing pain on Day 2 and Day 7 using PIN Questionnaire; number and 
percentage of participants reporting they were bothered or affected by the pain 
and local reactions based on the PIN Questionnaire; summary statistics of post-
injection pain assessment scores based on the NRS at Days 1, 2, and 7; number 
and percentage of participants for each pain assessment score from 0 to 10 
(0: 
 10: 
); number and percentage of participants reporting 
ISRs overall and by grade. Summary statistics of the duration of the ISRs 
overall and by grade. 
Part 2:  
• Summary statistics of post-infusion pain assessment scores based on the NRS at 
Days 1, 2, and 7. Number and percentage of participants for each pain 
assessment score from 0 to 10 (0: 
, 10: 
).  
• Intercurrent events (Part 1, Part 2, and Part 3):  
• Discontinuation from study for any reason: Treatment policy strategy will be 
applied to address this intercurrent event, as safety data will be collected at the 
follow-up visit and will be reported for all participants. 
Additional secondary questions of interest are: Part 1: What is the safety (based on 
additional secondary safety parameters) of a single 20 mg/kg SC dose of GSK3810109 
co-administered with rHuPH20 in healthy adults? Part 2: What is the safety (based on 
additional secondary safety parameters) of a single 60 mg/kg IV dose of GSK3810109 in 
healthy adults? Part 3: 
 
 
 
These secondary safety estimands are described by the following attributes: 
Population: Healthy male and female participants aged 18 to 65 years of age, inclusive. 
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• Treatment conditions:  
• Part 1: Single 20 mg/kg SC dose of GSK3810109 co-administered with rHuPH20.  
• Part 2: Single 60 mg/kg IV dose of GSK3810109.  
•
  
• Variables (Part 1, Part 2, and Part 3):  
• Change from baseline in laboratory assessments, ECGs, and vital sign 
measurements. 
• Summary measures (Part 1, Part 2 and Part 3):  
• Summary statistics for change from baseline in clinical laboratory assessments, 
electrocardiograms (ECGs) and vital sign measurements.  
• Intercurrent events (Part 1, Part 2, and Part 3): 
• Discontinuation from study for any reason: Treatment policy strategy will be 
applied to address this intercurrent event, as safety data will be collected at the 
follow-up visit and will be reported for all participants. 
Exploratory estimands 
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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is an open-label, single-dose study to assess the safety, tolerability, and PK of 
GSK3810109 administered SC with rHuPH20 or IV in healthy adult participants.  
This study will comprise 3 parts: 
In Part 1, approximately 8 participants will receive a single 20 mg/kg SC dose of 
GSK3810109 co-administered with rHuPH20 at dose of 2000 U/mL or ~28,000 U for a 
70 kg participant. The participants will be admitted in the clinic on Day –1 and the study 
product will be administered on Day 1. The participants will remain in the clinic for 
approximately 8 hours for study-related procedures after study product administration 
and will be followed up for 24 weeks.   
Safety laboratory samples will be collected throughout the study as per the SoA. The 
primary endpoint of ISR will be evaluated at specified time points up to Day 7; study 
participants will keep a diary of ISRs for 14 days after study product administration. 
Symptoms, maximum intensities, and durations will be reported through end of study to 
characterize presentation and resolution of local ISRs. 
Safety review decisions and the status of the enrollment process will be shared with the 
Safety Review Team (SRT) in regular intervals and discussed during the monthly SRT 
meetings. 
In Part 2, approximately 8 participants will receive a single 60 mg/kg IV dose of 
GSK3810109. A sentinel cohort of 2 participants will be used to mitigate the risk of 
unexpected AEs prior to dosing of the remaining 6 participants, who will be dosed in 
sequential cohorts of 2 participants each.  
The sentinel cohort of these 2 participants will be admitted to the clinic on Day –1. The 
study product will be administered on Day 1 and participants will remain in the clinic and 
be monitored for 7 days after study product administration. The participants will be 
discharged from the clinic on Day 8 and will be followed up for 24 weeks.  
Following Day 10 visit, core SRT will review the safety data (safety laboratory data, 
ECG, and AEs) from the sentinel cohort and may recommend continuation of the study 
where the next cohort of 2 participants will be dosed. 
The second cohort of 2 participants will be admitted to the clinic on Day –1. The study 
product will be administered on Day 1 and participants will remain in the clinic and be 
monitored for 7 days after study product administration. The participants will be 
discharged from the clinic on Day 8 and will be followed up for 24 weeks. A review of at 
least AE data from this cohort will be conducted after a minimum of 4 days following 
infusion of GSK3810109 and the core SRT may recommend continuation of the study 
where the next cohort of 2 participants will be dosed. 

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The third cohort of 2 participants will be admitted to the clinic on Day –1. The study 
product will be administered on Day 1 and participants will remain in the clinic and be 
monitored for 7 days after study product administration. The participants will be 
discharged from the clinic on Day 8 and will be followed up for 24 weeks. A review of at 
least AE data from this cohort will be conducted after a minimum of 4 days following 
infusion of GSK3810109 and the core SRT may recommend continuation of the study 
into the fourth cohort of 2 participants. 
The fourth cohort of 2 participants will be admitted to the clinic on Day –1. The study 
product will be administered on Day 1 and participants will remain in the clinic and be 
monitored for 7 days after study product administration. The participants will be 
discharged from the clinic on Day 8 and will be followed up for 24 weeks. 
Safety laboratory samples will be collected throughout the study as per the SoA. 
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4.2. 
Scientific Rationale for Study Design 
GSK3810109 is a human MAb active against HIV that can mediate extraordinary breadth 
and potency against various HIV isolates, including strains traditionally resistant to other 
antibodies in this class.  
This study is designed to evaluate safety, tolerability, and PK endpoints in healthy adult 
participants, when GSK3810109 is administered as either SC injection (Part 1 and Part 3 
of study) or IV infusion (Part 2 of study). The inclusion of both routes of administration 
in this study is an efficient design to enable rapid progression to future studies using 
either 1 or both routes of administration.  
The potency of GSK3810109 may indicate fewer antibodies are required to mediate an 
effect, offering the possibility of SC administration as a more feasible approach to 
immunoprophylaxis. The introduction of the leucine serine (LS) site-directed mutation to 
increase FcRn binding affinity is postulated to result in increased antibody half-life and 
persistence at biologically higher concentrations in the plasma, as was shown for 
VRC01LS and VRC07-523LS (Rudicell, 2014; Ko, 2014; Gaudinski, 2018). 
The rHuPH20 enzyme facilitates SC delivery of co‐administered therapeutics. The use of 
rHuPH20 with GSK3810109 offers the potential to administer a larger volume of the 
antibody than could be administered alone (~2.0 mL). Therefore, the current study will 
investigate the ability to deliver a larger SC dose of GSK3810109 (20 mg/kg, up to 
24 mL) in combination with rHuPH20. The rHuPH20 will be co-mixed with 
GSK3810109 at a concentration of 2000 U/mL based on the dosing volume of 
GSK3810109. 
In clinical studies to date for SC doses of rHuPH20 up to 30,000 U, systemic exposure 
has been undetectable Kirschbrown, 2018. 
 
 
 
There is a practical limitation for administration of high doses of GSK3810109 via SC 
infusion. To date, the maximum dose administered via SC route is 20 mg/kg, in 
combination with rHuPH20, while an IV route allows higher dose administration. In this 
study, an IV dose of 60 mg/kg of GSK3810109 will be administered, which offers the 
potential for an ultra-long-acting target profile to support administration every 4 to 
6 months, thus reducing dosing frequency and potentially improving adherence and 
acceptability. Medication adherence and decreasing frequency of clinic visits is the most 
important determinant for sustained viral suppression and long-term treatment success. 
This study is participant to the appropriate regulatory and ethics committee (EC) approval 
and will be listed on the website ClinicalTrials.gov. No blinding or placebo control will 
be used, as these are not necessary for the purposes of this study. 
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4.3. 
Justification for Dose 
This study will evaluate the safety and tolerability of a single SC 
 
 or IV dose of GSK3810109 
Part 1 
The dosages selected for evaluation of GSK3810109 are based on prior experience with 
another CD4-binding site antibody VRC01, which was shown in 2 clinical trials (VRC 
601 and VRC 602 [Ledgerwood, 2015; Lynch, 2015]) to be safe and well-tolerated at 5 to 
40 mg/kg dosages given IV and at a 5 mg/kg dosage given SC in both HIV-infected and -
uninfected adult populations. From prior experience in a FTIH study (VRC 609), 
GSK3810109 is also shown to be well-tolerated as a single dose at 5 mg/kg, 20 mg/kg, 
40 mg/kg IV, or 5 mg/kg SC and 5 mg/kg SC or 20 mg/kg IV by repeat dosing every 
12 weeks for a total of 3 injections/infusions.   
The VRC 609 study is now being conducted to evaluate a single 5 or 20 mg/kg dose of 
GSK3810109 (N6LS) co-mixed with rHuPH20 by SC infusion. As of 4 August 2021, no 
significant safety findings were noted. GSK3810109 was generally well tolerated, with 
no SAEs, dose-limiting toxicities, or deaths reported. The dose administered in this Part 
of the study will not exceed that in the FTIH study (VRC 609). 
The 20 mg/kg dose to be administered in the current study is based on the feasibility of 
delivering a SC dose with rHuPH20 within approximately 3 to 15 minutes via an infusion 
pump, as well as a comprehensive assessment of ISRs and acceptability of drug 
administration. The 20 mg/kg SC dose was chosen based the volume of administration, 
PK, and the safety data of repeat-dosing of 20 mg/kg IV administration which supports a 
possible SC 12-week dosing interval in combination with other antiretroviral agents to 
maintain viral suppression. A 12-week interval for repeat-dosing has also been used in 
clinical trials with IV administration of VRC01LS and VRC07-523LS. 
Part 2 
GSK3810109 belongs to the VRC01 class of CD4 binding site-directed bNAbs, which 
block HIV infection by occluding the binding site for the cellular receptor CD4. The N6 
antibody was modified by site-directed mutagenesis to increase its binding affinity for the 
FcRn to extend its half-life and is designated GSK3810109.  
The overall compartmental half-life (t1/2) of GSK3810109 is currently estimated to be 
44 ± 6 days for IV administration and offers the potential for an ultra-long-acting target 
profile. Ultra-long-acting ART, defined as 3 to 6 months or longer, can help to improve 
treatment adherence, which is the most important determinant for sustained viral 
suppression, a decrease in the frequency of clinic visits, and reduction in the social stigma 
associated with daily therapy. Based on PK estimates from the VRC 609 study and the 
antiviral effect of GSK3810109 at 280 mg in HIV viremic individuals in Study 207959 
(BANNER), it is estimated that a 40 mg/kg IV dosing may be able to provide coverage 
for 4 months but is unlikely to provide sufficient therapeutic breadth for a 6-month 
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dosing interval. Pharmacokinetic modelling suggests GSK3810109 given at 60 mg/kg 
may be adequate for every 6 months administration.  
A 60 mg/kg dose of GSK3810109 will exceed the 40 mg/kg no-observed-adverse-effect 
level (NOAEL) set by ViiV Healthcare. The NOAEL set by the VRC is at 400 mg/kg IV 
and has been endorsed by the FDA. Based on the same VRC generated data, ViiV set the 
NOAEL at 40 mg/kg due to the morbidity of 1 male rat at 400 mg/kg, for which it was 
not possible to exclude a relationship to exposure. A review of observed GSK3810109 
Cmax and area under the plasma concentration-time curve (AUC) exposure in humans at 
40 mg/kg IV found levels to be appreciably higher than rodent exposures at the 40 mg/kg 
NOAEL and raises questions of the relevancy of the rodent model PK as a basis for 
lowering the NOAEL from 400 mg/kg to 40 mg/kg. In addition, simulated PopPK 
modeling shows that 60 mg/kg IV in humans is predicted to have a lower Cmax than the 
VRC 400 mg/kg rat NOAEL Cmax. This model was used to simulate GSK3810109 
serum concentrations of 60 mg/kg IV dosing in a population of adults with a range of 
bodyweights representative of the anticipated volunteer population for Study 217901. 
Predicted individual serum concentration versus time profiles predict that after a 
60 mg/kg dose, serum concentrations of GSK3810109 in all individuals will be below the 
average Cmax from 40 mg/kg dosing within 3 days (i.e., 72 hours) of study product 
administration.  
No toxicologically relevant off-target binding was noted in tissue cross reactivity 
evaluation of adult human or rat tissues, and no staining was observed in any of the 
selected human neonatal tissues examined. Off-target safety review was performed by 
GSK using published scientific literature and a range of in silico tools; liver proliferation 
and increased mitochondria transmembrane potential were identified as theoretical risks 
for galectin-1 modulation. There were no indications of liver proliferation or 
mitochondria dysfunction in a repeat dose toxicology study where rats were given 
GSK3810109 on 3 occasions, 1 week apart up to 400 mg/kg IV. 
Based on these overall findings, dose escalation of GSK3810109 to 60 mg/kg IV could 
be acceptable with careful risk mitigation strategies. 
Safety data of human administration of GSK3810109 have found it to be safe. As of 
09 March 2022, GSK3810109 has been administered by IV or SC infusion/injection to 
38 HIV-uninfected adults and 14 treatment naïve HIV-infected adults and complete 
safety information is available in 36 participants. In all current studies, GSK3810109 has 
been found to be safe with no SAEs or deaths reported. All available clinical safety data 
relating to CD4 binding site class bNAbs and PK modelling data provide justification to 
conduct a Phase 1 study evaluating the safety and PK profile of IV 60 mg/kg dosing in 
HIV-uninfected adults. 
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4.4. 
End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the 
study or last scheduled procedure shown in the SoA (Section 1.5 , Section 1.6, and 
Section 1.7) for the last participant in the study. 
A participant is considered to have completed the study if he/she has completed all 
periods of the study and the last scheduled procedure shown in the SoA. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.  
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age 
1. Participant must be 18 to 65 years of age, inclusive, at the time of signing the 
informed consent. 
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Type of Participant and Disease Characteristics 
2. Participants who are overtly healthy as determined by medical evaluation 
including medical history, physical examination, laboratory tests, and without 
history of any of the conditions listed in the exclusion criteria. 
Weight 
3. Body weight must be 50 kg and <100 kg. 
Sex and Contraceptive/Barrier Requirements 
4. Male and/or female  
Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies. 
a. Participants who are female at birth are eligible to participate if at least one of the 
following conditions applies: 
• Not pregnant or breastfeeding and at least one of the following conditions applies: 
• Is not a participant of childbearing potential (POCBP). 
OR 
• Is a POCBP and agree to use contraceptive method as described in 
Section 10.4 from 3 weeks prior to the start of this study and during the study. 
The investigator should evaluate the effectiveness of the contraceptive method 
in relationship to the first dose of study intervention. 
• A POCBP must have a negative highly sensitive (see Section 10.4) serum 
pregnancy test on Day –1, prior to the first dose of study intervention. 
• Additional requirements for pregnancy testing during and after study intervention 
are located in Section 1.5 , Section 1.6, and Section 1.7. 
• All participants in the study should be counseled on safer sexual practices 
including the use and benefit/risk of effective barrier methods (e.g., male 
condom). 
• The investigator is responsible for review of medical history, menstrual history, 
and recent sexual activity to decrease the risk for inclusion of a POCBP with an 
early undetected pregnancy. 
Contraception Guidance and Collection of Pregnancy Information can be found in 
Section 10.4.2 and Section 10.4.3, respectively. 
Informed Consent 
5. Capable of giving signed informed consent as described in Section 10.1, which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 

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Other Inclusions 
6. Participants must have results that do not show clinically significant 
abnormalities, as judged by the investigator at screening. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Hypertension that is not well controlled as per investigator’s discretion. 
2. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, 
endocrine, hematological, or neurological disorders capable of significantly 
altering the absorption, metabolism, or elimination of drugs; constituting a risk 
when taking the study intervention or interfering with the interpretation of data. 
3. Positive HIV and/or hepatitis C antibody test  
4. Positive test result for SARS-CoV-2  
5. Evidence of hepatitis B virus infection at screening or within 3 months prior to 
first dose of study intervention 
• Participants positive for hepatitis B surface antigen (HBsAg) are excluded. 
• Participants negative for anti-HBs but positive for anti-HBc (negative 
HBsAg status) and positive for hepatitis B virus (HBV) DNA are excluded 
Note: Participants positive for anti-HBc (negative HBsAg status) and positive for 
anti-HBs (past and/or current evidence) are immune to HBV and are not excluded.  
6. Any history of a severe allergic reaction with generalized urticaria, angioedema or 
anaphylaxis within the 2 years prior to enrollment that has a reasonable risk of 
recurrence during the study. 
7. The participant has an underlying skin disease or disorder (i.e., infection, 
inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, 
urticaria) or tattoos that would interfere with assessment of injection sites. 
8. History of sensitivity to any of the study medications or their components or drugs 
of their class, or a history of drug or other allergy that, in the opinion of the 
investigator or medical monitor, contraindicates their participation. 
9. Clinically significant multiple or severe drug allergies, intolerance to topical 
corticosteroids, or severe post-treatment hypersensitivity reactions (including, but 
not limited to, erythema multiforme major, linear immunoglobulin A, dermatosis, 
toxic epidermal necrolysis, and exfoliative dermatitis). 
Prior/Concomitant Therapy 
10. Exposure to an experimental drug, human blood product, or vaccine (which does 
not have emergency, conditional, or standard market authorization) within 28 days 

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prior to the first dose of study treatment OR plans to receive live vaccines during 
the study 
Note: Consult with the Medical Monitor if clarification is needed. Receipt of a 
Coronavirus disease 2019 (COVID-19) vaccine that has received emergency, 
conditional, or standard market authorization is allowed if the investigator 
determines that the benefit-risk profile for that individual study participant is 
favorable. The use of other investigational COVID-19 vaccines that have not 
received emergency, conditional, or standard market authorization and are still 
only used in clinical trials will not be allowed at this time. 
Prior/Concurrent Clinical Study Experience 
11. Prior receipt of licensed or investigational MAb. 
12. Receipt of any investigational study agent within 28 days prior to first dose of 
study treatment 
13. Prior exposure to GSK3810109 or rHuPH20 in this or another clinical study. 
14. Where participation in the study would result in donation of blood or blood 
products in excess of 500 mL within 56 days. 
15. Exposure to more than 4 new chemical entities within 12 months prior to the first 
dosing day. 
Diagnostic Assessments 
16. Alanine aminotransferase (ALT) 1.5 times the upper limit of normal (ULN). 
17. Total bilirubin 1.5 times the ULN (isolated total bilirubin >1.5×ULN is 
acceptable if total bilirubin is fractionated and direct bilirubin <35%).  
18. Current or chronic history of liver disease or known hepatic or biliary 
abnormalities (with the exception of Gilbert's syndrome or asymptomatic 
gallstones) 
19. QTcF >450 msec for males and QTcF >470 msec for females. 
NOTES: 
• The QTc is the QT interval corrected for heart rate according to Fridericia’s 
formula (QTcF) machine-read or manually over-read. 
• QTcF will be used to determine eligibility and stopping/pause criteria for an 
individual participant in this study.  
20. The participant has a tattoo or other dermatological condition overlying potential 
injection sites that may interfere with interpretation of ISRs or administration of 
GSK3810109 
21. Grade 4 laboratory abnormalities 

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Other Exclusions 
22. Any other chronic or clinically significant medical condition that in the opinion of 
investigator would jeopardize the safety or rights of the participant including (but 
not limited to): diabetes mellitus type I, chronic hepatitis; OR clinically significant 
forms of drug or alcohol abuse, asthma, autoimmune disease, psychiatric 
disorders, heart disease, or cancer. 
23. Known hypersensitivity to hyaluronidase or any of the excipients in EDP. 
To assess any potential impact on participant eligibility with regard to safety, the 
investigator must refer to the IB and supplements, approved product labels, and/or local 
prescribing information for detailed information regarding warnings, precautions, 
contraindications, AEs, drug interactions, and other significant data pertaining to the 
study drugs. 
5.3. 
Lifestyle Considerations 
No lifestyle restrictions are required. 
5.3.1. 
Meals and Dietary Restrictions 
No dietary restrictions are required. 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
• There are no study-related restrictions on caffeine and tobacco. 
• During each dosing session, participants will abstain from alcohol for 24 hours before 
the start of dosing through Day 1. 
5.3.3. 
Activity 
• Participants will abstain from strenuous exercise for 24 hours before each blood 
collection for clinical laboratory tests.  
5.4. 
Screen Failures 
A screen failure occurs when a participant who consents to participate in the clinical 
study is not subsequently entered in the study. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to 
meet the Consolidated Standards of Reporting Trials publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, any protocol deviations, and any 
SAEs. 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened one time. Re-screened participants should be assigned a new 
participant number for re-screening. 

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5.5. 
Criteria for Temporarily Delaying  
Not applicable. 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY 
Study intervention is defined as any investigational intervention, marketed product, 
placebo, or medical device intended to be administered to a study participant according to 
the study protocol. 
6.1. 
Study Interventions Administered 
Table 1 
Study Interventions Administered 
Intervention Label 
 
 
Intervention on Label 
GSK3810109 
rHuPH20 
Intervention Description 
GSK3810109 is a clear, colorless 
to yellow liquid that is essentially 
free of visible particles; the product 
is supplied as a sterile aqueous 
buffered solution filled into 10 mL 
single-dose vials. 
Each vial of ENHANZETM Drug 
Product (EDP) contains 0.5 mL of 
rHuPH20 formulated at a 
concentration of 1 mg/mL 
(~110,000 U/mL rHuPH20).  EDP is 
manufactured by Ajinomoto Althea, 
Inc, (San Diego, CA) for Halozyme 
Therapeutics, Inc. (San Diego, CA) 
and is supplied in 2 mL glass vials 
as a sterile, single-dose, injectable 
liquid. 
Type  
Biologic 
Biologic 
Dose Formulation 
Vial 
Vial 
Unit Dose Strength  
600 mg/6mL vial 
Each vial of EDP contains 0.5 mL 
of rHuPH20 formulated at a 
concentration of 1 mg/mL 
(~110,000 U/mL rHuPH20) 
Dosage Level 
For Part 1, SC infusion 20 mg/kg  
For Part 2, IV infusion 60 mg/kg 
  
2000 U/mL based on dose of 
GSK3810109  
Route of Administration 
SC infusion/IV infusion 
SC infusion 
Use 
Experimental 
Experimental 
IMP and NIMP 
IMP 
IMP 
CCI

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Intervention Label 
 
 
Sourcing 
Provided by the sponsor 
Provided by the sponsor 
Packaging and Labeling 
Study intervention will be provided 
in vials. Each vial will be labeled as 
required per country requirement. 
Study intervention will be provided 
in vials. Each vial will be labeled as 
required per country requirement. 
Current/Former Name or 
Alias 
GSK3810109 /VH3810109/ N6LS 
Enhanze™ Drug Product (EDP) 
EDP = ENHANZETM Drug Product; IMP = investigational medicinal product; IV = intravenous; NIMP = 
non-investigational medicinal product.; SC = subcutaneous. 
6.2. 
Study Product Administration 
Subcutaneous Administration with rHuPH20 
The SC administration site(s) to be used must be assessed as acceptable by the clinician 
and the participant. The preferred SC administration site is the abdomen. GSK3810109 
will be mixed with rHuPH20 in the pharmacy and then administered via standard 
Medfusion 3500 syringe pump (or equivalent) in 1 infusion site at a rate of no more than 
3 mL/minute. For Part 1, given the weight criterion in this study, the maximum volume 
needed to administer a 20 mg/kg SC dose is not expected to exceed 24 mL. 
 
 
. If the participant experiences side effects during 
the infusion, the rate of infusion may be slowed or stopped to alleviate the symptoms. 
Intravenous Administration  
For Part 2, participants will receive IV administration of GSK3810109. The IV access 
will be placed in an arm vein in an aseptic manner. A different site should be used for 
collection of PK blood samples; however, the same site may be used after flushing the 
line if another site is not available. GSK3810109 will be diluted with normal saline to 
infuse approximately 250 mL of solution at the appropriate concentration (as described in 
the current IB [Investigator’s Brochure]) over about 60 minutes. The entire infusion 
should not exceed 2 hours. If the participant experiences side effects during the infusion, 
the rate of infusion may be slowed or interrupted to alleviate the symptoms. 
There are no pre-medications for IV administration; however, based on emerging safety 
data from sentinel participants, these may be given at the investigator’s discretion and in 
consultation with the Medical Monitor. 
Study Product and Administration Regimen 
GSK3810109 is a clear, colorless to yellow liquid, that is essentially free of visible 
particles; the product is supplied as a sterile aqueous buffered solution filled into 10 mL 
single-dose vials. Each vial contains a 6.25 ± 0.10 mL volume of GSK3810109 at a 
concentration of 100 ± 10 mg/mL in a formulation buffer composed of 10 mM sodium 
citrate, 50 mM sodium chloride, 150 mM arginine-hydrochloride, and 0.002% 
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polysorbate-80 at pH 6.5. Vials have a nominal fill volume of 6.25 mL to enable 
withdrawal up to 6.0 mL. 
In calculating the dose to administer and number of vials to thaw, it should be assumed 
that the concentration is 100 mg/mL and that a volume of at least 6 mL can be withdrawn 
from a vial. In this study, dose is limited or established based on participant weight. For 
example, for a participant weighing 100 kg (the upper limit per protocol eligibility) who 
receives a 20 mg/kg dose, the GSK3810109 amount needed is calculated as follows: 
100 kg × 20 mg/kg = 2000 mg of GSK3810109, which corresponds to 20 mL of the 
100 mg/mL solution. Since each product vial contains at least 6 mL, 4 vials will be 
needed for the dose preparation for this participant. 
Refer to Pharmacy Manual for specific handling, preparation, and administration 
instructions. 
6.3. 
Preparation, Handling, Storage and Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited to 
the investigator and authorized site staff. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records). 
Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff. In the case of unintentional 
occupational exposure notify the monitor, Medical Monitor, and/or ViiV/GSK study 
contact. 
A Material Safety Data Sheet/equivalent document describing occupational hazards and 
recommended handling precautions either will be provided to the investigator, where this 
is required by local laws, or is available upon request from ViiV/GSK. 
The detailed guidance and information on preparation, handling, storage, and 
accountability is provided in the Study Reference Manual. 
6.4. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label study. Study product will be administered sequentially to the 
participants in Part 2 and Part 3 (Section 4.1 and Section 1.6, and Section 1.7). 

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6.5. 
Study Intervention Compliance 
GSK3810109 will be administered to participants either SC with rHuPH20 or IV at the 
study site. Administration will be documented in the source documents and reported in 
the electronic case report form (eCRF) 
6.6. 
Overdose 
For this study, any administered dose of GSK3810109 and/or rHuPH20, greater than that 
intended for the study will be considered an overdose. 
The investigator should use clinical judgment in treating overdose, as ViiV Healthcare is 
unable to recommend specific treatment other than supportive care. 
In the event of an overdose, the investigator/treating physician should: 
1. Contact the Medical Monitor immediately. 
2. Monitor vital signs regularly for several hours after the overdose. 
3. Closely monitor the participant for AE/SAE and laboratory abnormalities until 
GSK3810109 can no longer be detected systemically. 
4. Obtain a sample for PK analysis from the date of the overdose of study 
intervention if requested by the Medical Monitor (determined on a case-by-case 
basis). 
5. Document the quantity of the excess dose as well as the duration of the 
overdosing in the eCRF. 
Since this is a single-dose administration of GSK3810109, dose modifications will not be 
applicable. However, if the participant experiences side effects during the infusion, the 
rate of infusion may be slowed or stopped to alleviate the symptoms. 
6.7. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrollment or receives during the study must be recorded along with: 
• reason for use 
• dates of administration including start and end dates 
• dosage information including dose and frequency 
Concomitant medications (prescription and non-prescription) should be administered 
only as medically necessary during the study. All concomitant medications, blood 
products, and vaccines (clinicians should work with participants regarding the timing of 
licensed vaccines relative to study product administration) taken during the study will be 
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Non-protocol defined treatments or medical interventions (e.g., physical therapy, 
radiotherapy, surgical procedures) are permitted during the study for appropriate medical 
management of the participant.  
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
Emerging safety data will be reviewed in-stream as the study progresses and the 
following criteria will result in a study pause. A full safety review will be conducted, and 
the findings and recommendations presented to ViiV Safety and Labelling Committee 
(VSLC) for endorsement: 
• Any SAE, regardless of its severity, that is considered be clinically significant and 
reasonably attributable to dosing with GSK3810109, in the opinion of the 
investigator and sponsor. 
• Acute allergic reaction or CRS (Division of AIDS [DAIDS] criteria Grade 3 to 4) 
reasonably attributable to dosing with GSK3810109, in the opinion of the 
investigator and sponsor. 
• Any AE of Grade 4 intensity assessed as related to GSK3810109, as reported by 
the investigator. 
• Any participant meeting liver chemistry stopping criteria (see Section 7.2) 
• Any participant meeting QTcF stopping criteria (see Section 7.3) 
• If 2 participants in any discrete part of the study (Part 1, Part 2, or Part 3) 
experience an AE of Grade 3 intensity (excluding ISRs) assessed as related by the 
investigator. 
• If 2 or more injections/infusions administered in any discrete part of the study 
(Part 1, Part 2, or Part 3) are followed by an ISR of at least Grade 3 in severity. 
Note: Grade 3 ISRs that are based on the size of erythema or induration alone will 
not be considered as a pausing criterion. However, any Grade 3 ISR of erythema 
or induration due to ulceration, secondary infection, phlebitis, sterile abscess, 
drainage, or symptoms causing inability to perform usual social and functional 
activities (as per DAIDS) will be included as a pausing criterion. 
Relevant reporting and discussion with the Medical Monitor, relevant study team 
personnel, and the institutional review board (IRB)/independent ethics committee (IEC) 
will take place before resumption of dosing. Every effort will be made to take a blood 
sample at the time of the AE for PK analysis. 

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7.2. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to assure 
participant safety and evaluate liver event etiology (in alignment with the FDA 
pre-marketing clinical liver safety guidance [DHHS, 2009]). 
Discontinuation of GSK3810109 is not possible for abnormal liver tests as this is a 
single-dose study. If a participant meets liver chemistry stopping criteria, the study will 
pause to conduct an evaluation of the relevant safety data. The findings and 
recommendations on dosing resumption will be presented to VSLC for endorsement. 
Liver Chemistry Stopping Criteria 
• ALT ≥3 × ULN 
• If ALT ≥3 × ULN AND bilirubin 2 × ULN (>35% direct bilirubin) or 
international normalized ration >1.5, report as an SAE. 
 
Refer to Section 10.5 for required Liver Safety Actions and Follow up Assessments. 
7.3. 
QTcF Stopping Criteria 
If a participant meets the below mentioned QTcF stopping criteria, the study will pause to 
conduct an evaluation of the relevant safety data. The findings and recommendations on 
dosing resumption will be presented to VSLC for endorsement. 
QTcF Stopping Criteria: 
• QTcF > 480 msec, 
• Change from baseline: QTcF >60 msec 
7.4. 
Participant Discontinuation/Withdrawal from the Study 
• A participant may withdraw from the study at any time at his/her own request or 
may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral, or compliance reasons. This is expected to be uncommon. 
• At the time of discontinuing from the study, if possible, an early discontinuation 
visit should be conducted, as shown in the SoA. See SoA for data to be collected 
at the time of study discontinuation and follow-up and for any further evaluations 
that need to be completed. 
• If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent. 
• If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records. 

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7.5. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are handled as part of 
Section 10.1.9. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Section 1.5, 
Section 1.6, and Section 1.7). 
• Protocol waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with the sponsor immediately 
upon occurrence or awareness. 
• Adherence to the study design requirements, including those specified in the SoA, 
is essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that 
potential participants meet all eligibility criteria. The investigator will maintain a 
screening log to record details of all participants screened and to confirm 
eligibility or record reasons for screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management 
(e.g., blood count) and obtained before signing of ICF may be utilized for 
screening or baseline purposes provided the procedure met the protocol-specified 
criteria and was performed within the timeframe defined in the SoA. 
• The maximum amount of blood collected from each participant over the duration 
of the study, including any extra assessments that may be required, will not 
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• Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 
8.1. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA.  
8.1.1. 
Physical Examinations 
• A complete physical examination will include, at a minimum, assessment of skin, 
head, ears, eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular system, 
abdomen, lymph nodes, and musculoskeletal system/extremities. A brief physical 
examination will include at minimum, assessment of skin, lungs, cardiovascular 
system, and abdomen [liver and spleen]). For Part 2, a brief physical examination 
will also be performed within 30 to 60 minutes of end of infusion (EOI). 
• Height and weight will also be measured and recorded. Shoes should be removed 
for height and weight measurements. 
• Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
8.1.2. 
Vital Signs 
• Vital signs will be measured in a supine position after the participant has been at 
rest for at least 5 minutes in a quiet setting without distractions (e.g., television, 
cell phones) and will include body temperature, systolic and diastolic blood 
pressure, respiratory rate, and pulse. 
• For Part 1, on Day 1, the vital signs and SPO2 will be measured at predose and at 
4 hours and 8 hours postdose. 
• For Part 2, on Day 1, the vital signs and SPO2 will be measured at predose, every 
15 minutes from start of infusion for 2 hours, and at 4 hours and 8 hours postdose.  
• For Part 3, on Day 1, the vital signs and SPO2 will be measured at predose and at 
4 hours and 8 hours postdose.  
8.1.3. 
Electrocardiograms 
• 
Triplicate 12-lead ECG will be obtained in a supine position as outlined in the 
SoA (Section Section 1.5, Section 1.6 and Section 1.7) using an ECG machine 
that automatically calculates the heart rate and measures PR, QRS, QT, and 
QTcF intervals. The ECG taken at Screening and on Day 1 before study product 
administration will be a single reading; however, repeat ECGs are allowed at 
investigator’s discretion to confirm the eligibility. Triplicate 12-lead ECG will 
be obtained for all postdose time points. For Part 2, for Visit 01A, ECGs will be 
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• 
The ECG should be read locally and be centrally archived. Please contact the 
Medical Monitor if any concerns.  
8.1.4. 
Clinical Safety Laboratory Tests 
• 
Refer to Section 10.2 for the list of clinical laboratory tests to be performed and 
to the SoA (Section 1.5, Section 1.6 and Section 1.7) for the timing and 
frequency.  
• 
The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the eCRF. The laboratory reports must be filed with the source 
documents.  
• 
Clinically significant abnormal laboratory findings are those which are not 
associated with the underlying disease, unless judged by the investigator to be 
more severe than expected for the participant’s condition. 
• 
All laboratory tests with values considered clinically significantly abnormal 
during participation in the study should be repeated until the values return to 
normal or baseline or are no longer considered significantly abnormal by the 
investigator or Medical Monitor. If such values do not return to normal/baseline 
within a period of time judged reasonable by the investigator, the etiology 
should be identified and the sponsor notified. 
• 
All protocol-required laboratory assessments, as defined Section 10.2 must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.5, 
Section 1.6 and Section 1.7), through the central laboratory. 
8.1.5. 
Pregnancy Testing 
• Details of all pregnancies in female participants at birth will be collected after the 
start of study intervention and until completion of the long-term follow-up period. 
• If a pregnancy is reported, the investigator should inform ViiV/GSK within 
24 hours of learning of the pregnancy and should follow the procedures outlined 
in Section 10.4.3. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
8.1.6. 
COVID-19 Measures 
The measures approved for implementation within this clinical study to protect 
participant safety, welfare, and rights, and to ensure data integrity and the integrity of the 
clinical study, as a result of COVID-19 only, are outlined in Section 10.6. 

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8.2. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Other Safety Reporting 
The definitions of an AE or SAE can be found in Section 10.3. As described in Appendix 
3 (Section 10.3) intensity of AEs (and laboratory abnormalities) will be graded using the 
DAIDS grading table. 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the study (see Section 7). 
For AEs related to COVID-19, please see Section 10.6.5.2.  
8.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from the start of study intervention until the last visit 
at the time points specified in the SoA (Section 1.5 , Section 1.6, and 
Section 1.7). However, any SAEs assessed as related to study participation (e.g., 
study intervention, protocol-mandated procedures, invasive tests, or change in 
existing therapy) or related to a ViiV/GSK product will be recorded from the 
time a participant consents to take part in the study. 
• 
All AEs will be collected from the start of intervention until last study visit at 
the time points specified in the SoA (Section 1.5 ,Section 1.6, and Section 1.7). 
• 
Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded in the Medical History/Current 
Medical Conditions section of the eCRF not the AE section. 
• 
All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Section 10.3.4. The investigator will submit any updated SAE data to the 
sponsor within 24 hours of it being available. 
• 
Investigators are not obligated to actively seek AEs or SAEs after the conclusion 
of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the 
study, and he/she considers the event to be reasonably related to the study 
intervention or study participation, the investigator must promptly notify the 
sponsor. 
8.2.2. 
Method of Detecting AEs and SAEs 
• 
The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Section 10.3. 

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• 
Care will be taken not to introduce bias when detecting AE and/or SAE. 
Open-ended and non-leading verbal questioning of the participant is the 
preferred method to inquire about AE occurrence. 
8.2.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, and non-serious AEs of special 
interest, will be followed until the event is resolved, stabilized, otherwise explained, or 
the participant is lost to follow-up (as defined in Section 7.5). Further information on 
follow-up procedures is given in Section 10.3.3. 
8.2.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of an SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study intervention under clinical investigation are 
met.  
• 
The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
IRB/ IEC, and investigators. 
• 
Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions according to local regulatory requirements and sponsor policy 
and forwarded to investigators as necessary. 
• 
An investigator who receives an investigator safety report describing an SAE or 
other specific safety information (e.g., summary or listing of SAE) from the 
sponsor will review and then file it along with the IB and will notify the 
IRB/IEC, if appropriate according to local requirements. 
8.2.5. 
Pregnancy 
• Details of all pregnancies in female participants at birth will be collected after the 
start of study intervention and until completion of the long-term follow-up period. 
• If a pregnancy is reported, the investigator will record pregnancy information on 
the appropriate form and submit it to ViiV/GSK within 24 hours of learning of the 
female participant or female partner of male participant (after obtaining the 
necessary signed informed consent from the female partner) pregnancy. While 
pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
• The participant/pregnant female partner will be followed to determine the 
outcome of the pregnancy. The investigator will collect follow-up information on 

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the participant/pregnant female partner and the neonate, and the information will 
be forwarded to the sponsor. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 10.3. While the investigator is not obligated to actively seek this 
information in former study participants/pregnant female partner, he or she may 
learn of an SAE through spontaneous reporting. 
• Any female participant who becomes pregnant while participating in the study 
will be withdrawn from the study. 
8.2.6. 
Adverse Events of Special Interest 
Adverse events of special interest include: ISRs (only for Part 1 and Part 3), infusion-
related reactions, and serious/severe immune reactions (including anaphylaxis and CRS). 
8.2.7. 
Specific Toxicities/Adverse Event Management 
8.2.7.1. 
Injection/ Infusion Site Reactions (ISRs) 
All ISRs will be graded using the DAIDS grading table. Injection or infusion site 
reactions will be managed through investigator assessment throughout the study. All ISRs 
that are either serious, Grade 3 or higher, or persisting beyond 7 days must be discussed 
with the Medical Monitor to determine etiology and assess appropriate continued study 
participation. 
Digital photographs will be documented in all participants who have an ISR. 
Dermatology may be consulted for all participants who have an ISR considered serious, 
Grade 3 or above, or if clinically significant and persistent beyond 30 days and others if 
the investigator or Medical Monitor feels it is medically necessary. Grade 3 ISR 
consisting of erythema alone will not require dermatology consultation, but will be at the 
discretion of the investigator. 
Details regarding photo collection and any other follow up will be given by the Medical 
Monitor at the time of assessment. 
Injection/infusion site erythema or swelling will be evaluated and graded using the 
measured surface area (using the calculation of diameter/2 × length/2 × Pi [3.14]) and 
data regarding the size of these ISRs recorded at each ISR measurement (width and 
length). 
Injection/infusion site reaction discomfort can be managed symptomatically (e.g., 
cold/warm compress, acetaminophen, ibuprofen) if the reaction is interfering with the 
participant’s ability to perform activities of daily living. The required intervention should 
be documented on the appropriate eCRF page. 
For Part-2, infusion site reaction will be collected in the form of AE only. 

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Diary Cards (applicable to only Part 1 and Part 3) 
Participants will complete a diary card following GSK3810109 injection. This allows 
participants to record and score the severity of any reactions, record the impact of the 
injection on normal daily activities as well as any action taken such as use of analgesic 
medication following the injection. 
Participants will be required to bring the original completed diary cards to the next clinic 
visit and hand over to the investigator/site staff who will enter the information from the 
ISR diary cards into the relevant ISR Diary section of the eCRF within the same 
timeframe as normal eCRF data entry. 
PIN Questionnaire (applicable to only Part 1 and Part 3) 
Dimension score “acceptance of ISRs” and individual item score assessing pain will be 
evaluated by PIN Questionnaire. Refer to Section 10.9, Appendix 9 for PIN 
Questionnaire. 
NRS Questionnaire 
Post-injection/infusion pain assessment will be scored as specified in the SoA 
(Section 1.5, Section 1.6, and Section 1.7) by NRS from 0 to 10 (0: 
, 10: 
 
). Refer to Section 10.8, Appendix 8 for NRS. 
8.3. 
Pharmacokinetics 
Whole blood samples of approximately 2 mL will be collected for measurement of 
concentrations of GSK3810109 and rHuPH20 as specified in the SoA (Section 1.5, 
Section 1.6, and Section 1.7). 
• The timing of PK samples may be altered and/or PK samples may be obtained at 
additional time points during the study to ensure thorough PK monitoring if 
warranted and agreed upon between the investigator and the sponsor. 
• Instructions for the collection and handling of biological samples will be provided 
by the sponsor. The actual date and time (24-hour clock time) of each sample will 
be recorded. 
• Samples will be used to evaluate the PK of GSK3810109. Each blood sample will 
be processed into serum and divided into 2 aliquots (1 each for PK and a 
back-up). Samples collected for analyses of GSK3810109 serum concentration 
may also be used to evaluate safety or efficacy aspects related to concerns arising 
during or after the study. 
• PK Samples will be analyzed using an appropriately validated assay method by or 
under the supervision of the sponsor. 
• For Part 3,
 
 
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8.4. 
Genetics 
Genetics are not evaluated in this study. 
8.5. 
Immunogenicity Assessments 
Antibodies to GSK3810109 will be evaluated in serum samples collected from all 
participants according to the SoA (Section 1.5, Section 1.6, and Section 1.7). 
Additionally, serum samples should also be collected at the final visit from participants 
who were withdrawn from the study. These samples will be tested by the sponsor or 
sponsor’s designee. 
Serum samples will be screened for antibodies binding to GSK3810109 and the titer of 
confirmed positive samples will be reported. Other analyses may be performed to verify 
the stability of antibodies to GSK3810109 and/or further characterize the 
immunogenicity of GSK3810109. 
The detection and characterization of antibodies to GSK3810109 will be performed using 
a validated assay method by or under the supervision of the sponsor. Samples collected 
for detection of antibodies to study intervention may also be evaluated for GSK3810109 
serum concentration as described in Section 8.3 to enable interpretation of the antibody 
data. Antibodies may be further characterized and/or evaluated for their ability to 
neutralize the activity of the study intervention. Genetic analyses will not be performed 
on these serum samples. Participant confidentiality will be maintained. 
Samples may be stored according to local regulations following the last participant’s last 
visit for the study at a facility selected by the sponsor to enable further analysis of 
immune responses to GSK3810109. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
Analyses will be performed separately for each study part, and will be the same across 
study parts, unless otherwise stated.  
There is no formal research hypothesis that will be statistically tested in this study. 
9.1.1. 
Multiplicity Adjustment 
There is no multiplicity adjustment required for this study. 

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9.2. 
Analysis Sets 
For the purposes of analysis, the following analysis sets are defined: 
Analysis Set 
Description 
Screened 
All participants who will be screened for eligibility.  
Enrolled 
All participants who sign the ICF. 
Note that screening failures (who never passed screening even 
if rescreened) and participants screened but never enrolled 
into the study (met eligibility but not needed) are excluded 
from the Enrolled Analysis Set as they did not enter the study.  
Safety 
All participants who receive at least 1 dose of study 
intervention. 
PK Concentration 
Participants who receive at least 1 dose of study intervention 
and have at least 1 assayed postdose sample of PK 
concentration data. This analysis population will be used in 
the assessment and characterization of PK concentrations. 
PK Parameter 
All participants in the PK population who received study 
intervention for whom valid and evaluable serum PK 
parameters are derived. This analysis population will be used 
in the assessment and characterization of PK parameters. 
ICF = informed consent form; PK = pharmacokinetic(s) 

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9.3. 
Statistical Analyses 
9.3.1. 
General Considerations 
The SAP will be finalized prior to database lock and it will include a more technical and 
detailed description of the statistical analyses described in this section, as well as to 
provide details of any additional planned analyses. This section is a summary of the 
planned statistical analyses of the primary, secondary, and exploratory endpoints. 
9.3.2. 
Primary Endpoints/Estimands Analysis 
All safety analyses will be performed on the Safety Analysis Set. 
The severity of AEs and SAEs will be determined by the investigator (Section 10.3). All 
reported AEs will be coded using MedDRA and summarized by system organ class and 
preferred term. Estimands are presented in Section 3. 
The number and percentage of participants with treatment-emergent AEs, SAEs, study 
product-related AEs, deaths, and AEs leading to study product or study withdrawal 
through Week 24 will be provided. The number and percentage of participants with 
elevated Grade 2 to 4 ALT or elevated Grade 2 to 4 AST values will be provided. The 
number and percentage of participants with treatment-emergent AEs will also be 
summarized by severity (grade), including (for Part 1 and Part 3) a categorization for AEs 
Grade 2 or higher. For Part 1 and Part 3, the number and percentage of participants who 
have ISRs within 7 days following study treatment administration will be provided.   
Categorical results will be summarized using frequency measures (number and 
percentage) and numerical results will be summarized using descriptive statistics (eg., 
mean, standard deviation, minimum. median, maximum). 
Additional analyses may be performed to further characterize the primary endpoints and 
will be detailed in the SAP. 
9.3.3. 
Secondary Endpoints/Estimands Analysis 
9.3.3.1. 
Pharmacokinetic Analysis 
Serum GSK3810109 concentration-time data will be analyzed by PPD, under the 
oversight of Clinical Pharmacology Modeling & Simulation department within 
GSK/ViiV, using non-compartmental methods with Phoenix® WinNonlin® Version 8.0 or 
higher. Statistical analysis will be performed by PPD, under the oversight of Biostatistics, 
GSK/ViiV. Calculations will be based on the actual sampling times recorded during the 
study. Estimands are presented in Section 3. 
Based on the individual concentration-actual time data the following serum PK 
parameters for GSK3810109 will be estimated as data permit: 
AUC(0-inf) – Area under the plasma concentration-time curve from time zero 
extrapolated to infinity 

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AUC(0-t) – Area under the plasma concentration-time curve from time zero to time of 
last observed quantifiable concentration 
Cmax – Maximum observed concentration 
Tmax – Time of maximum observed concentration 
t1/2 – Apparent terminal phase half-life  
Summary statistics (arithmetic mean, geometric mean, median, standard deviation, 
minimum, maximum, and coefficient of variation) will be summarized. 
Other PK parameters, e.g. clearance, volume of distribution at steady state, and volume of 
distribution may also be derived as appropriate. 
Blood concentration-time data from different parts of the study may be analyzed using a 
population approach. A non-linear mixed effects model will be used to determine 
population PK parameters and identify relevant covariates (e.g., age, weight, or disease 
related covariates). The data from this study may be combined with the data from other 
studies for a population PK analysis, which will be reported separately. 
Further details of the PK analysis will be provided in the SAP. 
9.3.3.2. 
Safety Analysis 
Estimands are presented in Section 3. 
For Part 1 and Part 3 only:  
Analyses related to the severity and acceptance of pain and ISRs will be performed on the 
Safety Analysis Set. 
Dimension scores “acceptance of ISRs” and individual item scores assessing pain at 
Day 2 and Day 7 using the PIN questionnaire data will be summarized using descriptive 
statistics. Number and percentage of participants reporting they were bothered or affected 
by the pain and local reactions based on the PIN Questionnaire will be provided for 
Day 2 and Day 7. Number and percentage of participants reporting ISRs overall and by 
grade will be provided. The duration of the ISRs will be summarized overall and by 
grade. Additional analyses may be performed to further characterize the secondary 
endpoints related to the severity and acceptance of pain and ISRs, and will be detailed in 
the SAP. 
For Parts 1, 2, and 3 separately:  
Post injection/infusion pain assessment scores based on a NRS from 0 to 10 (0: 
, 
10: 
) will be summarized by the study day using descriptive statistics and 
also as the number and percentage of participants for each pain assessment score. 
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Change from baseline over time in laboratory parameters, ECGs, and vital signs will be 
summarized with descriptive statistics. For ECG values, the frequency in different 
categories of maximum post-baseline QTcF values, including maximum change from 
baseline in QTcF, will be provided. Details about the categories of maximum 
post-baseline QTcF values and maximum change from baseline in QTcF will be included 
in the SAP. 
The frequency of laboratory abnormality events along with the shift from baseline to the 
worst-case post-baseline value will be provided. Abnormal liver chemistry results will be 
determined using increases above the ULN. Change from baseline values will be 
summarized with descriptive statistics. 
Categorical results will be summarized using frequency measures (number and 
percentage) and numerical results will be summarized using descriptive statistics (eg., 
mean, standard deviation, minimum. median, maximum). Further details of the safety 
analysis will be provided in the SAP.  
 
Additional analyses may be performed to further characterize the secondary safety 
endpoints and will be detailed in the SAP. 
9.3.4. 
Exploratory Endpoints/Estimands Analysis 
 
 
Anti-drug antibodies to GSK3810109 will be monitored in the study. Further details of 
the analysis will be provided in the SAP. 
9.4. 
Interim Analysis 
An interim analysis is planned after all participants receiving SC administration in Part 1 
complete their Week 24 visit. At that timepoint, the data available for participants 
receiving IV administration will also be analyzed and included. This interim analysis is 
planned to enable a preliminary assessment of the safety and PK of this compound to be 
used for the planning of future studies.  
Further details will be provided in the SAP. 
9.5. 
Sample Size Determination 
The number of participants in this study is based on clinical and practical considerations 
and not on a formal statistical power calculation. The total sample size of approximately 
8 participants in each part is considered sufficient for the objectives of the study. 
A sufficient number of participants will be enrolled to ensure approximately 
8 participants complete each part of the study for a total of approximately 24 participants 
in the study. 
Participants who withdraw prior to study completion may be replaced. 
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with: 
o Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) international ethical 
guidelines 
o Applicable International Council for Harmonisation (ICH) Good Clinical 
Practice (GCP) guidelines 
o Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated.  
• Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
• Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• The investigator will be responsible for the following: 
o Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC 
o Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures 
o Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, 
the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations. 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 

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10.1.3. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study, 
including the risk and benefits, to the participant and answer all questions 
regarding the study. 
• Participants must be informed that their participation is voluntary. Participants 
will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, privacy and data 
protect requirements, where applicable, and the IRB/IEC or study center. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study.  
• A copy of the ICF(s) must be provided to the participant. 
• Participants who are rescreened are required to sign a new ICF. 
• If follow-up information from a treating physician or other licensed medical 
practitioner is required for a medical device incident with an AE/SAE involving 
an associated person(s), the Associated Person Safety Reporting Information and 
Authorization Letter must be signed by the associated person to obtain consent. 
• GSK/ViiV Healthcare (alone or working with others) may use participant’s coded 
study data and samples and other information to carry out this study; understand 
the results of this study; learn more about GSK3810109 or about the study 
disease; publish the results of these research efforts; work with government 
agencies or insurers to have the GSK3810109 approved for medical use or 
approved for payment coverage.  
10.1.4. 
Data Protection 
• Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information that would make the participant 
identifiable will not be transferred. 
• The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant who will be required to give 
consent for their data to be used as described in the informed consent. 
• The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed by 
the sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 

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10.1.5. 
Committees Structure 
An SRT for GSK3810109 reviews emerging and cumulative data for GSK3810109 on a 
monthly basis. For Part 1, safety review decisions and the status of the enrollment process 
will be shared with an SRT at regular intervals and discussed during the monthly SRT 
meetings. 
For Part 2, a core SRT for Study 217901 study will review data for both sentinel and 
non-sentinel participants of the study. For Part 3, the core SRT will review data for the 2 
participants in the first cohort before enrolling the next 6 participants. The core SRT is 
composed of safety lead, medical monitors, and project biostatistician.  
The SRT will make recommendations to the VSLC regarding safety findings, including 
study pause, modification, and termination. The VSLC is chaired by the ViiV Chief 
Medical Officer and will have the final decision on study modifications, including 
termination. Details regarding the VSLC membership and function are included within 
the VSLC Charter. 
10.1.6. 
Dissemination of Clinical Study Data 
• Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report. The investigator 
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
ViiV/GSK site or other mutually agreeable location. 
• ViiV/GSK will also provide all investigators who participated in the study with a 
summary of the study results and will tell the investigators what treatment their 
patients received. The investigator is encouraged to share the summary results 
with the study participants, as appropriate. 
• Under the framework of the SHARE initiative, ViiV/GSK intends to make 
anonymized participant-level data from this study available to external 
researchers for scientific analyses or to conduct further research that can help 
advance medical science or improve patient care. This helps ensure the data 
provided by study participants are used to maximum effect in the creation of 
knowledge and understanding. Requests for access may be made through 
www.clinicalstudydatarequest.com. 
• The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with ViiV/GSK Policy. 
10.1.7. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic 
Case Report Forms (CRFs) unless transmitted to the sponsor or designee 
electronically (e.g., laboratory data). This includes accurate and timely 
transcription of the data recorded on the participant-completed ISR diary cards 
(applicable to Part 1 and Part 3 of the study) into the relevant section of the study 

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eCRF. The investigator is responsible for verifying that data entries are accurate 
and correct by physically or electronically signing the CRF.  
• Guidance on completion of eCRFs will be provided in eCRF Completion 
Guidelines. 
• Quality tolerance limits (QTLs) will be pre-defined in the QTL report to identify 
systematic issues that can impact participant safety and/or reliability of study 
results. These pre-defined parameters will be monitored during and at the end of 
the study and all deviations from the QTLs and remedial actions taken will be 
summarized in the clinical study report. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• Monitoring details describing strategy including definition of study critical data 
items and processes (e.g., risk-based initiatives in operations and quality such as 
risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities and requirements, including handling of non-compliance 
issues and monitoring techniques (central, remote, or on-site monitoring) are 
provided in the monitoring plan. 
• The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. Detailed information about study data 
collection and management process including systems used can be found in the 
study Data Management Plan. 
• The sponsor assumes accountability for actions delegated to other individuals 
(e.g., contract research organizations). 
• Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
clinical study report/equivalent summary unless local regulations or institutional 
policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. 
10.1.8. 
Source Documents 
• Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• Data reported on the eCRF or entered in the eCRF that are transcribed from 
source documents must be consistent with the source documents or the 
discrepancies must be explained. This includes the participant-completed ISR 
diary cards (source documents) and the data transcribed from the dairy cards into 
the eCRF. The investigator may need to request previous medical records or 
transfer records, depending on the study. Also, current medical records must be 
available. 

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• Definition of what constitutes source data, and its origin can be found in [Source 
Data Acknowledgment]. 
• The investigator must maintain accurate documentation (source data) that 
supports the information entered on the eCRF. 
• Study monitors will perform ongoing source data verification to confirm that data 
entered onto the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are 
being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements. 
10.1.9. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first participant screened and will be the study start 
date. 
Study/Site Termination 
ViiV/GSK or designee reserves the right to close the study site or terminate the study at 
any time for any reason at the sole discretion of ViiV/GSK. Study sites will be closed 
upon study completion. A study site is considered closed when all required documents 
and study supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
For study termination: 
• Discontinuation of further study intervention development 
For site termination: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate or no recruitment of participants (evaluated after a reasonable amount 
of time) by the investigator. 
• If the study is prematurely terminated or suspended, the sponsor shall promptly 
inform the investigators, the IECs/IRBs, the regulatory authorities, and any 
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suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the participant and should assure appropriate 
participant therapy and/or follow-up. 
10.1.10. 
Publication Policy 
• The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.  
• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by 
mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 

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10.2. 
Appendix 2: Clinical Laboratory Tests 
The tests detailed in Table 2 will be performed by the central laboratory/the local 
laboratory.  
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol. 
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations. 
Table 2 
Protocol-required Safety Laboratory Tests 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet count  
Red Blood Cell count 
Hemoglobin 
Hematocrit 
Red Blood Cell Indices: 
Mean corpuscular volume  
Mean corpuscular hemoglobin 
% Reticulocytes 
White Blood Cell 
count with 
differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Clinical 
Chemistry1 
Blood Urea Nitrogen 
Creatinine 
Glucose (fasting) 
Potassium  
Sodium 
Chloride  
Calcium 
Carbon dioxide 
AST 
ALT  
Alkaline phosphatase2 
Total and direct 
bilirubin 
Albumin 
Total protein 
Routine 
Urinalysis 
• Specific gravity 
• pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, 
leukocyte esterase by dipstick 
• Microscopic examination (if blood or protein is abnormal on dipstick) 
Pregnancy 
testing 
• Highly sensitive serum human chorionic gonadotropin (hCG) pregnancy 
test (as needed for women of childbearing potential) 
Other Screening 
Tests 
• Test for SARS-CoV-2  
• Follicle-stimulating hormone (as needed in women of non-childbearing 
potential only) 
• Urine drug screen (alcohol, amphetamines, barbiturates, 
benzodiazepines, cannabinoids, cocaine metabolites, cotinine, 
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Laboratory 
Assessments 
Parameters 
[including heroin, codeine, and oxycodone]) 
• HIV-1 and -2 antigen/antibody immunoassay, Hepatitis B (HBsAg), 
anti-HBc, (aHBcT), anti-HBsAg, HBV DNA (as needed) and hepatitis C 
antibody3 
NOTES : 
1. 
Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping or 
monitoring event are given in Section 10.5. All events of ALT 3 × upper limit of normal (ULN) and total bilirubin 
2 × ULN (>35% direct bilirubin) or ALT 3 × ULN and international normalized ratio (INR) >1.5, if INR measured, 
which may indicate severe liver injury (possible Hy’s law), must be reported to ViiV/GSK in an expedited manner 
(excluding studies of hepatic impairment or cirrhosis). 
2. 
If alkaline phosphatase is elevated, consider fractionating. 
3. 
HBV DNA will only be performed for participants with a positive anti-HBc and negative HBsAg and negative anti-
HBs (past and/or current evidence). 

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10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study intervention. 
 
Definition of Unsolicited and Solicited AE 
• An unsolicited AE is an AE that was not solicited using a participant diary and that is 
communicated by a participant who has signed the informed consent. Unsolicited 
AEs include serious and non-serious AEs. 
• Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, emergency room visit, or visit to/by a healthcare 
provider). The participants will be instructed to contact the site as soon as possible to 
report medically attended event(s), as well as any events that, though not medically 
attended, are of participant concern. Detailed information about reported unsolicited 
AEs will be collected by qualified site personnel and documented in the participant’s 
records. 
• Unsolicited AEs that are not medically attended nor perceived as a concern by the 
participant will be collected during an interview with the participants and by review 
of available medical records at the next visit. 
• Solicited AEs are predefined local at the injection site and systemic events for which 
the participant is specifically questioned, and which are noted by the participant in 
their diary. 
 

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Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (i.e., not related to progression of 
underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New condition detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention 
interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae. 
 
Events NOT Meeting the AE Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 
 

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10.3.2. 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. 
• This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g., sprained ankle) that may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations: 
• Possible Hy’s Law case: ALT ≥3 × ULN AND total bilirubin ≥2 × ULN (>35% 
direct bilirubin) or international normalized ratio >1.5 must be reported as an 
SAE. 
• Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations such as 
significant medical events that may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in 
the above definition. These events should usually be considered serious. 
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An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
intensive treatment for allergic bronchospasm, blood dyscrasias, 
convulsions, or development of intervention dependency or intervention 
abuse. 
10.3.3. 
Recording and Follow-up of AEs and SAEs 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• The investigator will then record all relevant AE/SAE information. 
• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to ViiV/GSK in lieu of completion of the ViiV/GSK required form. 
• There may be instances when copies of medical records for certain cases are 
requested by ViiV/GSK. In this case, all participant identifiers, with the exception of 
the participant number, will be redacted on the copies of the medical records before 
submission to ViiV/GSK. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to one of the following categories:  
• Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• Moderate: Minimal, local or non-invasive intervention indicated; limiting 
age-appropriate instrumental Activities of Daily Living (ADL). Instrumental ADL 
refers to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
• Severe: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting 
self-care ADL. Self-care ADL refers to bathing, dressing and undressing, feeding 
self, using the toilet, taking medications, and not bedridden. 
 
 

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Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine the relationship. 
• A reasonable possibility of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The investigator will also consult the IB and/or Product Information, for marketed 
products, in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to ViiV/GSK. However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to ViiV/GSK. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 

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Follow-up of AE and SAE 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by 
ViiV/GSK to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health-care professionals. 
• If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide ViiV/GSK with a copy of any postmortem 
findings including histopathology.  
• New or updated information will be recorded in the originally submitted documents. 
• 
The investigator will submit any updated SAE data to ViiV/GSK within 24 hours of 
receipt of the information. 
 
10.3.4. 
Reporting of SAE to ViiV/GSK 
SAE Reporting to ViiV/GSK via Electronic Data Collection Tool 
• The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see next 
section) or to the Medical Monitor/SAE coordinator by telephone. 
• 
Contacts for SAE reporting can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page. 
 

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SAE Reporting to ViiV/GSK via Paper Data Collection Tool 
• Facsimile transmission of the SAE paper data collection tool is the preferred method 
to transmit this information to the Medical Monitor or the SAE coordinator. 
• In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service. 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE data collection tool within the designated reporting time 
frames. 
• Contacts for SAE reporting can be found at this beginning of the protocol on the 
Sponsor/Medical Monitor Contact Information page. 

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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions: 
Participants of Childbearing Potential (POCBPs) 
A female at birth is considered fertile following menarche and until becoming 
post-menopausal unless permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 
Participants in the following categories are not considered POCBPs. 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other 
than the above, (e.g., Müllerian agenesis, androgen insensitivity), investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the 
participant’s medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause.  
o A high follicle-stimulating hormone (FSH) level in the 
postmenopausal range will be used to confirm a postmenopausal state 
in women not using hormonal contraception or hormonal replacement 
therapy (HRT). In the absence of 12 months of amenorrhea, 
confirmation with more than 1 FSH measurement is required.  
• Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-estrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study. Otherwise, they must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment. 

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10.4.2. 
Contraception Guidance: 
Participants of childbearing potential are eligible to participate if they agree to use a 
method of contraception consistently and correctly as described in Table 3. 
Table 3 
Highly Effective Contraceptive Methods 
CONTRACEPTIVES1 ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methods2 That Have Low User Dependency Failure rate of <1% per year 
when used consistently and correctly. 
• 
Implantable progestogen-only hormone contraception associated with inhibition of ovulation2 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)2 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner: 
Note: Vasectomized partner is a highly effective contraceptive method provided that the partner 
is the sole sexual partner of the participant of childbearing potential and the absence of sperm 
has been confirmed. If not, an additional highly effective method of contraception should be 
used. Spermatogenesis cycle is approximately 90 days. 
Highly Effective Methods2 That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly. 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation3 
• oral 
• intravaginal 
• transdermal 
• injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulation3 
• oral 
• injectable 
• 
Sexual abstinence 
• Note: Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with 
the study intervention. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the study and the preferred and usual lifestyle of the participant. 
ACCEPTABLE METHODS4 
• 
Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary 
mode of action 
• 
Male or female condom with or without spermicide5 
• 
Cervical cap, diaphragm, or sponge with spermicide 
• 
A combination of male condom with either cervical cap, diaphragm, or sponge with spermicide 
(double-barrier methods)3 
1. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
2. 
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
3. 
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contraceptive methods are limited to those that inhibit ovulation as the primary mode of action. 
4. 
Considered effective, but not highly effective - failure rate of ≥1% per year. Periodic abstinence (calendar, 
sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational 
amenorrhoea method (LAM) are not acceptable methods of contraception. 
5. Male condom and female condom should not be used together (due to risk of failure with friction). 
10.4.3. 
Collection of Pregnancy Information: 
Male participants with partners who become pregnant 
• 
Investigator will attempt to collect pregnancy information on any female partner 
of a male study participant who becomes pregnant while he is participating in 
this study. This applies only to male participants who receive study intervention. 
• 
After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to ViiV/GSK within 24 hours of learning of the 
partner’s pregnancy.  
• 
The female partner will also be followed to determine the outcome of the 
pregnancy. Information on the status of the mother and child will be forwarded to 
ViiV/GSK. 
• 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of 
fetal status (presence or absence of anomalies) or indication for procedure.  
Female participants who become pregnant 
• 
Investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. 
• 
The initial information will be recorded on the appropriate form and submitted to 
ViiV/GSK within 24 hours of learning of a participant's pregnancy. 
• 
Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on participant and neonate, which 
will be forwarded to ViiV/GSK. Generally, follow-up will not be required for 
longer than 6 to 8 weeks beyond the estimated delivery date. 
• 
Any termination of pregnancy will be reported, regardless of fetal status 
(presence or absence of anomalies) or indication for procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. 
• 
A spontaneous abortion (occurring at <22 weeks gestational age) or still birth 
(occurring at >22 weeks gestational age) is always considered to be an SAE and 
will be reported as such. 
• 
Any SAE occurring as a result of a post-study pregnancy, which is considered 
reasonably related to the study intervention by the investigator, will be reported 

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to ViiV/GSK as described in Section 10.3. While the investigator is not obligated 
to actively seek this information in former study participants, he or she may learn 
of an SAE through spontaneous reporting.  
• 
Any female participant who becomes pregnant while participating will 
discontinue study intervention or be withdrawn from the study. 

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10.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments 
A liver stopping event is an occurrence of pre-defined liver chemistry changes (ALT, 
bilirubin) that trigger pause of study and requirement of additional actions and follow up 
assessments to be performed. 
 
 
Liver Chemistry Stopping Criteria  
 
ALT-absolute 
 
ALT ≥3 × ULN 
If ALT ≥3 × ULN AND bilirubin1,2 2 × ULN (>35% direct bilirubin) or INR >1.5, report as an 
SAE. 
See additional Actions and Follow-up Assessments listed below 
Required Actions and Follow-up Assessments  
Actions 
Follow-up Assessments 
• 
Immediately pause study 
• 
Report the event to ViiV/GSK within 24 hours 
• 
Complete the liver event eCRF, and complete an SAE 
data collection tool if the event also meets the criteria 
for an SAE2 
• 
Perform liver event follow-up assessments 
• 
Monitor the participant until liver chemistries resolve, 
stabilize, or return to within baseline (see 
MONITORING below) 
MONITORING: 
If ALT ≥3 × ULN AND bilirubin ≥2 × ULN or INR >1.5 
• 
Repeat liver chemistries (include ALT, AST, alkaline 
phosphatase, bilirubin, and INR) and perform liver 
event follow-up assessments within 24 hours 
• 
Monitor participant twice weekly until liver chemistries 
resolve, stabilize or return to within baseline 
• 
A specialist or hepatology consultation is 
recommended 
If ALT ≥3 × ULN AND bilirubin <2 × ULN and INR ≤1.5: 
• 
Repeat liver chemistries (include ALT, AST, alkaline 
phosphatase, bilirubin and INR) and perform liver 
event follow-up assessments within 24 to 72 hours 
• 
Monitor participant weekly until liver chemistries 
resolve, stabilize or return to within baseline 
• 
Viral hepatitis serology3 
• 
Obtain INR and recheck with each liver chemistry 
assessment until the aminotransferase values show 
downward trend 
• 
Obtain blood sample for PK analysis, obtained 
within 48 hours of last dose4  
• 
Serum creatine phosphokinase and lactate 
dehydrogenase 
• 
Fractionate bilirubin, if total bilirubin ≥2 × ULN 
• 
Obtain complete blood count with differential to 
assess eosinophilia 
• 
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, on the 
AE report form 
• 
Record use of concomitant medications on the 
concomitant medications report form including 
acetaminophen, herbal remedies, other 
over-the-counter medications 
• 
Record alcohol use on the liver event alcohol intake 
eCRF 
If ALT ≥3 × ULN AND bilirubin ≥2 × ULN or INR >1.5: 
• 
Anti-nuclear antibody, anti-smooth muscle antibody, 
Type 1 anti-liver kidney microsomal antibodies, and 
quantitative total immunoglobulin G or gamma 
globulins. 
• 
Liver imaging (ultrasound, magnetic resonance, or 
computerized tomography) and /or liver biopsy to 
evaluate liver disease; complete liver imaging 
and/or liver biopsy eCRF. 

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1. 
Serum bilirubin fractionation should be performed if testing is available. Additionally, if serum bilirubin fractionation 
testing is unavailable, record presence of detectable urinary bilirubin on dipstick, indicating direct bilirubin 
elevations and suggesting liver injury. 
2. 
All events of ALT 3 × ULN and bilirubin 2 × ULN (>35% direct bilirubin) or ALT 3 × ULN and INR >1.5, which 
may indicate severe liver injury (possible “Hy’s Law”), must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis); the INR threshold value stated will not apply to participants receiving anticoagulants. 
3. 
Includes: hepatitis A immunoglobulin (IgM) antibody, hepatitis B surface antigen, and hepatitis B core antibody; 
hepatitis C RNA; cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, 
obtain heterophile antibody or monospot testing) and hepatitis E IgM antibody. 
4. 
Pharmacokinetic sample may not be required for participants known to be receiving placebo or non- ViiV/GSK 
comparator interventions. Record the date/time of the PK blood sample draw and the date/time of the last dose of 
study intervention prior to PK blood sample draw in the eCRF. If the date or time of the last dose is unclear, 
provide the participant’s best approximation. If the date/time of the last dose cannot be approximated OR a PK 
sample cannot be collected in the time period indicated above, do not obtain a PK sample. Instructions for sample 
handling and shipping are in the Study Reference Manual. 

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10.6. 
Appendix 6: COVID-19 Pandemic and Clinical Study 
Continuity 
The COVID-19 pandemic may impact the conduct of clinical studies. Significant 
logistical challenges may arise from quarantines, variable restrictions on site resources 
and operations, site closures, travel limitations and the inability of an individual 
participant to attend clinic visits, interruptions to the supply chain for the investigational 
product, or other considerations if site personnel or study participants become infected 
with COVID-19. These challenges may lead to difficulties in meeting protocol-specified 
procedures, including dispensation of the investigational product to the participant or 
adhering to protocol-mandated visits and laboratory/diagnostic testing. 
Based on these challenges, it may be necessary to adopt additional measures and 
procedures to protect participant safety, and to ensure that there are no gaps in study 
treatment for participants enrolled in this clinical study. 
In order to maintain the scientific integrity of the study and adhere to updated guidance 
from regulators, procedures have also been put into place to ensure that the actions taken 
to mitigate against any impact of COVID-19 are well documented in the study database. 
This appendix outlines the measures that are approved for implementation within this 
clinical study, to protect participant safety, welfare, and rights, and to ensure data 
integrity and the integrity of the clinical study, as a result of COVID-19 only. These 
measures may be implemented in accordance with any requirements and expectations set 
out by local IRBs/IECs and National Competent Authorities, as necessary. 
This appendix does not apply to participant management issues that are unrelated to a 
specific, and documented, impact from COVID-19. 
10.6.1. 
Changes to Study Visits and Study Procedures 
• If central laboratory testing cannot be performed at a particular visit, and monitoring 
for safety is required, tests may be performed at an appropriately 
authorized/accredited local laboratory (or other relevant clinical facility), if this can 
be done within local restrictions on physical distancing. The site should proactively 
inform the sponsor about such instances. Local laboratory results may be used to 
inform safety decisions. Results should be retained in source records. 
• When on-site visits are reduced, it is important that the investigator continue 
collecting relevant clinical information, including AEs, from the participant through 
alternative means, e.g., by telephone contact. 
• There may be cases where the current principal investigator of a site is indisposed for 
a period and may need to delegate parts of his or her duties temporarily, e.g., to a 
sub-investigator. Any such changes should be documented in the site’s source 
records. Any permanent changes in principal investigator should be communicated to 
the sponsor. 

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• There may also be circumstances where immediate actions are required by the 
sponsor and/or investigator, outside of what is contemplated in the protocol, in order 
to protect a study participant from immediate hazard. Any such measures will be 
carefully documented and conducted in accordance with the National Competent 
Authority/IRB/IEC regulations. 
10.6.2. 
Changes to Informed Consent 
Informed consent should continue per normal procedure and as described in the main 
body of the protocol, to the extent possible. However, there may be circumstances where 
re-consent of participants is needed, and a physical signature on site is not possible. In 
these cases, alternative ways of obtaining such re-consent should be considered, such as 
the participant sending a picture of his/her written consent to the investigator, or the 
investigator contacting the participant by telephone or video call and obtaining verbal 
consent, supplemented with email confirmation.   
Any updated ICF or other participant-facing materials should be provided to participants 
by e-mail, mail or courier before re-consent is obtained. Any consent obtained this way 
should be documented in source records and confirmed by way of normal consent 
procedure at the earliest opportunity when participants attend their next on-site study 
visit. 
Any alternative informed consent procedure must be undertaken only after site IRB/EC 
agreement and approval. 
10.6.3. 
COVID-19 Vaccines 
Any active study participant who has access via local guidelines to a COVID-19 vaccine 
that has received emergency, conditional, or standard market authorization may receive 
that vaccine, if requested by the site investigator and study participant. 
Ideally, when COVID-19 vaccinations are given, administration should occur at least 
2 weeks before or after a study visit to allow for a distinctive assessment of any possible 
ISRs. 
As of January 2021, there is limited publicly available information on the reduction of 
severe acute respiratory syndrome coronavirus-2 transmission after vaccination. 
Therefore, until further evidence is available and/or local guidance changes, COVID-19 
precautions (e.g., masking, social distancing) should be maintained after a vaccination 
series is completed. 
10.6.4. 
COVID-19 Experimental Agents 
If any treatments for COVID-19 are planned for a study participant, please consult with 
the study Medical Monitor to ensure that relevant drug interactions are considered and to 
ensure that continued study participation remains appropriate. 

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10.6.5. 
COVID-19 Specific Data Capture 
10.6.5.1. 
Capturing COVID-19-Specific Protocol Deviations 
Please refer to the Study Reference Manual for specific details on capturing protocol 
deviations as a result of COVID-19. 
10.6.5.2. 
Capturing COVID-19 Specific Adverse Events and Serious Adverse 
Events 
ViiV Healthcare/GSK is monitoring the evolving situation with respect to COVID-19 
carefully and the impact this may have on ongoing or planned clinical studies. It is 
important for the study team to describe COVID-19-related AEs/SAEs and their impact 
on study data and outcomes. Standardization of case definitions will facilitate future data 
analyses. 
Please use the following guidance: 
1. Adverse events should continue to be evaluated as to whether they meet SAE criteria 
as defined in the protocol, and if so, submitted according to established SAE 
reporting requirements. Serious AEs and AEs should be submitted following usual 
study procedures and timelines. 
2. When an in-person clinic visit is not possible, please conduct a remote telehealth visit 
to assess for, and document any AEs/SAEs. 
3. Investigators should use the World Health Organization definition to classify 
COVID-19 cases. The definition below, released March 20, 2020, represents a time 
point for standardized collection. We recognize definitions are likely to continue to 
evolve; the most recent definitions should be consulted for each case When reporting 
both serious and non-serious AEs (related to COVID-19 infection), investigators 
should use the following verbatim terms: 
a. Suspected COVID-19 infection; or 
b. Probable COVID-19 infection; or 
c. Confirmed COVID-19 infection.  
4. Sites should contact the study Medical Monitor for questions related to definitions, 
reporting, and decisions around the impact to study drug continuation in the setting of 
clinically defined mild COVID-19 infection. 
5. A new COVID-19 infection eCRF will be included to collect additional details about 
the reported COVID-19 AE or SAE data. It is important that the correct information 
is collected from each participant reporting a COVID-19 AE or SAE. Therefore, 
please use the eCRF templates to help you collect this information for all 
COVID-19-related AEs/SAEs. 

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World Health Organization Case Definition  
March 20, 2020 Version (https://www.who.int/publications-detail/global-surveillance-
for-human-infection-with-novel-coronavirus-(2019-ncov) 
Suspected case:  
A. A participant with acute respiratory illness (fever and at least one sign/symptom 
of respiratory disease, e.g., cough, shortness of breath) AND a history of travel to 
or residence in a location reporting community transmission of COVID-19 
disease during the 14 days prior to symptom onset; 
OR 
B. A participant with any acute respiratory illness AND having been in contact (see 
definition of “COVID-19 contact” below) with a confirmed or probable 
COVID-19 case (see definition of “contact”) in the last 14 days prior to symptom 
onset; 
OR 
C. A participant with severe acute respiratory illness (fever and at least 
1 sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND 
requiring hospitalization) AND in the absence of an alternative diagnosis that 
fully explains the clinical presentation. 
Probable case:  
A. A suspect case for whom testing for the COVID-19 virus is inconclusive 
(inconclusive being the result of the test reported by the laboratory); 
OR  
B. A suspect case for whom testing could not be performed for any reason. 
Confirmed case: 
A person with laboratory confirmation of COVID-19 infection, irrespective of clinical 
signs and symptoms. 
COVID-19 Contact: 
A contact is a person who experienced any one of the following exposures during the 
2 days before and the 14 days after the onset of symptoms of a probable or confirmed 
case: 
1. Face-to-face contact with a probable or confirmed case within 1 meter and for more 
than 15 minutes; 
2. Direct physical contact with a probable or confirmed case; 
3. Direct care for a patient with probable or confirmed COVID-19 disease without using 
proper personal protective equipment; OR 
4. Other situations as indicated by local risk assessments. 

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Note: For confirmed asymptomatic cases, the period of contact is measured as the 2 days 
before through the 14 days after the date on which the sample was taken, which led to 
confirmation. 

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10.7. 
Appendix 7: Division of AIDS Table for Grading the Severity 
of Adult and Pediatric Adverse Events Corrected 
Version 2.1, July 2017 
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (DAIDS, 2017) is a descriptive terminology that can be utilized for AE reporting. 
A grading (severity) scale is provided for each AE term. 
The table will be used as posted at the link above with the following exemptions: 
• Weight loss will be recorded as an AE only if it is considered deleterious to the 
participant’s health. 
• For severity grading of the solicited bruising parameter at the product 
administration site, the definitions based on size of the largest diameter and listed 
for the “Injection Site Erythema or Redness” will be used. The severity grade 
definition for “Bruising” provided under the Dermatologic Clinical Conditions 
will be used only for unsolicited adverse events involving bruising at other body 
locations. 
• Creatinine changes will be graded on the basis of the upper limit of normal 
provided by the grading table and not change from baseline. 
• Creatinine clearance changes will be graded according to mL/minute provided by 
the grading table and not change from baseline. 
• Subclinical comprehensive metabolic panel results for sodium, potassium, 
chloride, bicarbonate, BUN, and glucose will not be considered an AE unless 
Grade 2 or greater. 
Estimating Severity Grade for Parameters Not Identified in the Grading Table 
The functional table below should be used to grade the severity of an AE that is not 
specifically identified in the grading table. In addition, all deaths related to an AE are to 
be classified as Grade 5. 
Parameter 
Grade 1 Mild 
Grade 2 Moderate 
Grade 3 Severe 
Grade 4 Potentially 
Life-Threatening 
Clinical adverse 
event NOT identified 
elsewhere in the 
grading table 
Mild symptoms 
causing no or 
minimal interference 
with usual social & 
functional activities 
with intervention not 
indicated 
Moderate symptoms 
causing greater than 
minimal interference 
with usual social & 
functional activities with 
intervention indicated 
Severe symptoms 
causing inability to 
perform usual social & 
functional activities 
with intervention or 
hospitalization 
indicated 
Potentially life-threatening 
symptoms causing inability 
to perform basic self-care 
functions with intervention 
indicated to prevent 
permanent impairment, 
persistent disability, or death 
 

T M F -1 4 9 6 5 2 3 5  
C O N FI D E N TI A L  
 
 
2 1 7 9 0 1  
 
Pr ot oc ol A m d 2  
1 0 6  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V1 6 d at e d  2 4 -J u n -2 0 2 1  
 
1 0. 8.  
A p p e n di x 8 : N u m eri c R ati n g S c al e  
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d 
b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

T M F -1 4 9 6 5 2 3 5  
C O N FI D E N TI A L  
 
 
2 1 7 9 0 1  
 
Pr ot oc ol A m d 2  
1 0 7  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V1 6 d at e d  2 4 -J u n -2 0 2 1  
 
1 0. 9.  
A p p e n di x 9: PI N Q u e sti o n n air e ( F or P art 1 a n d P art 3 o nl y)  
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or 
i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

T M F -1 4 9 6 5 2 3 5  
C O N FI D E N TI A L  
 
 
2 1 7 9 0 1  
 
Pr ot oc ol A m d 2  
1 0 8  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V1 6 d at e d  2 4 -J u n -2 0 2 1  
 
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s 
or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n 
e x cl u d e d.

T M F -1 4 9 6 5 2 3 5  
C O N FI D E N TI A L  
 
 
2 1 7 9 0 1  
 
Pr ot oc ol A m d 2  
1 0 9  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V1 6 d at e d  2 4 -J u n -2 0 2 1  
 
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or 
i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

T M F -1 4 9 6 5 2 3 5  
C O N FI D E N TI A L  
 
 
2 1 7 9 0 1  
 
Pr ot oc ol A m d 2  
1 1 0  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V1 6 d at e d  2 4 -J u n -2 0 2 1  
 
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or 
i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

T M F -1 4 9 6 5 2 3 5  
C O N FI D E N TI A L  
 
 
2 1 7 9 0 1  
 
Pr ot oc ol A m d 2  
1 1 1  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V1 6 d at e d  2 4 -J u n -2 0 2 1  
 
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s 
or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n 
e x cl u d e d.

T M F -1 4 9 6 5 2 3 5  
C O N FI D E N TI A L  
 
 
2 1 7 9 0 1  
 
Pr ot oc ol A m d 2  
1 1 2  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V1 6 d at e d  2 4 -J u n -2 0 2 1  
 
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or 
i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

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10.10. 
Appendix 10: Abbreviations and Trademarks 
AE 
Adverse event 
ADL 
Activities of Daily Living 
AIDS 
Acquired immunodeficiency syndrome 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ART 
Antiretroviral therapy 
AST 
Aspartate aminotransferase 
AUC 
Area under the plasma concentration-time curve 
AUC(0-inf) 
Area under the plasma concentration-time curve from 
time zero extrapolated to infinity 
AUC(0-t) 
Area under the plasma concentration-time curve from 
time zero to time of last observed quantifiable 
concentration 
bNAb 
Broadly-neutralizing monoclonal antibody 
CA 
Competent Authority 
CI 
Confidence interval 
CFR 
Code of Federal Regulations 
Cmax 
Maximum observed concentration  
COVID-19 
Coronavirus disease 2019 
CRF 
Case report form 
CRS 
Cytokine release syndrome 
D 
Day 
DAIDS 
Division of AIDS 
EC 
Ethics committee 
ECG 
Electrocardiogram  
eCRF 
Electronic case report form 
EDP 
ENHANZE™ Drug Product 
EOI 
End of Infusion 
FcRn 
Neonatal Fc-receptor 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
FTIH 
First-time-in-human 
GCP 
Good Clinical Practice 
gp120 
glycoprotein 120 subunit 
GSK 
GlaxoSmithKline  
HA 
Hyaluronan 
CCI

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HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HIV 
Human immunodeficiency virus-1 
HRT 
Hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICF 
Informed consent form  
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee  
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
IRB 
Institutional Review Board  
ISR 
Injection site reaction 
IV 
Intravenous (ly) 
LS 
Leucine serine 
MAb 
Monoclonal antibody 
NOAEL 
no-observed-adverse-effect level 
NIMP 
Non-investigational medicinal product 
NRS 
Numeric rating scale 
PIN 
Perception of injection 
PK 
Pharmacokinetic(s) 
POCBP 
Participant of childbearing potential 
PSRT 
Protocol Safety Review Team 
QD 
Once daily 
QTLs 
Quality tolerance limits 
QTc 
Corrected QT interval 
QTcF 
QT interval corrected for heart rate according to 
Fridericia’s formula 
QTL 
Quality tolerance limit 
rHuPH20 
Recombinant human hyaluronidase PH20  
SC 
Subcutaneous (ly) 
SAE 
Serious adverse event  
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
Severe acute respiratory syndrome-related coronavirus-2 
SoA 
Schedule of activities 
SOI 
Start of Infusion 
SRT 
Safety Review Team 
t1/2 
Apparent terminal phase half-life 
Tmax 
Time of maximum observed concentration  

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ULN 
Upper limit of normal  
UNAIDS 
Joint United Nations Programme on HIV/AIDS 
VSLC 
ViiV Safety and Labelling Committee 
VRC 
Vaccine Research Center 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
NONE 
 
DAIDS 
 
 
Darzalex Faspro 
 
 
EDP 
 
 
Herceptin Hylecta 
 
 
HyQvia/ HYQVIA 
 
 
Mabthera 
 
 
Phesgo 
 
 
Phoenix 
 
 
Rituxan 
 
 
Rituxan Hycela 
 
 
WinNonlin 
 
 
 
 

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10.11. 
Appendix 11: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents. 
Amendment 01: 03-Jun-2022 
Overall Rationale for the Amendment 01: The protocol is amended to include an 
additional dosing group (Part 2) which will include 8 new healthy participants who will 
receive a single 60 mg/kg dose of GSK3810109 administered intravenously.  
Section # and Name Description of Change 
Brief Rationale 
Throughout the 
document, as 
applicable  
Sections were modified to 
accommodate IV administration of 
GSK3810109 designated as Part 2 
of the study and language was 
updated to clarify procedures 
applicable only for SC 
administration, now designated as 
Part 1 of the study. 
To clarify 8 new participants will be 
included in the study who will 
receive a single 60 mg/kg dose of 
GSK3810109 administered 
intravenously. 
1.1 Synopsis and 
10.1.5 Committees 
Structure 
SRT composition was modified, 
and text was edited. 
To reflect correct composition and to 
provide more clarity. 
Section 5.2 
Exclusion criteria 
Following exclusion criterion was 
added:  
Positive test result for 
SARS-CoV-2. 
This exclusion criterion was not 
previously included although a 
negative SARS-CoV-2 test was 
required prior to entry by the clinic. 
Section 10.8 
Appendix: Numeric 
Rating Scale 
One of the NRS examples was 
removed.  
The removed example of NRS was 
not being used in the study. 
Throughout the 
document 
Minor formatting and language 
changes were made. 
For clarity and better readability. 

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11. 
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