Clinical trial NCT05174013
Conditions: Pain
Keywords: Pharmacokinetics Safety Tolerability GSK3858279 Placebo Caucasian Chinese Japanese
Sponsor: GlaxoSmithKline
Start date: 2022-02-14; Completion date: 2023-04-17
Enrollment: 33 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), target engagement (TE) and immunogenicity of GSK3858279 when administered to healthy Caucasian, Chinese and Japanese participants.

Detailed description:

Arms: arm 1: Participants received 240 milligrams (mg) of GSK3858279 administered as separate subcutaneous (SC) injection to healthy Caucasian participants. arm 2: Participants received 240 mg of GSK3858279 administered as separate SC injection to healthy Chinese participants. arm 3: Participants received 240 mg of GSK3858279 administered as separate SC injection to healthy Japanese participants. arm 4: Participants received single dose of Placebo administered as separate SC injection to healthy Caucasian participants. arm 5: Participants received Single dose of Placebo administered as separate SC injection to healthy Chinese participants. arm 6: Participants received Single dose of Placebo administered as separate SC injection to healthy Japanese participants.
Interventions: intervention 1: GSK3858279 intervention 2: Placebo
Intervention descriptions: intervention 1: GSK3858279 will be administered intervention 2: Placebo will be administered

Protocol documents:
Prot_000.pdf: 
TMF-14597981 
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GlaxoSmithKline group of companies 
 
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TITLE PAGE 
Protocol Title A Randomised, Double-blind, Placebo-controlled Study of the Safety, 
Tolerability, Pharmacokinetics, Target Engagement and Immunogenicity of a single 
subcutaneous dose of GSK3858279 administered to Healthy Caucasian, Chinese and 
Japanese Participants.  
Protocol Number: 212979/ Amendment 02 
Compound Number  GSK3858279 
Brief Title: Safety, tolerability, pharmacokinetics and target engagement of 
GSK3858279 after a single subcutaneous dose in healthy Caucasian, Chinese and 
Japanese participants  
Study Phase: Phase 1  
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Regulatory Agency Identifying Number(s): TBC 
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual 
Sponsor Signatory: 
Dr Nicolas Wisniacki (MD, PhD) 
VP Head of Discovery Medicine, Clinical Pharmacology and 
Experimental Medicine 
Approval Date: 29 Apr 2022 
 
 
 
 
©2022 GSK group of companies or its licensor. All rights reserved.  Unauthorised 
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 
29 Apr 2022 
TMF-14597981 
Amendment 01 
11-JAN-2022 
TMF-14393139 
Original Protocol 
16-Nov-2021 
TMF-13921276 
 
Amendment 2 29 Apr 2022 
Overall Rationale for the Amendment:  
This is a protocol amendment with changes to the inclusion criteria, extension of time 
window for PK and TE samples taken post Day 113, changes to the extended follow up 
to make visits after Day 113 optional for Chinese and Japanese participants, updates to 
the Schedule of Activities table, removal of Covid stopping criteria and a minor update of 
the Risk Assessment table with respect to Covid Contingency Planning. These 
amendments were made following feedback from the study site and changes to internal 
guidance at GSK.   
 
 
 


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Section and 
Name  
Description of Change 
Brief Rationale 
Global change 
Update through out to specify 
visits after Day 113 are 
mandatory for Caucasian 
participants. 
To aid with participant recruitment and 
compliance to the study schedule 
Objectives and 
Endpoints 
Secondary endpoint (evaluation 
of TE) updated to include fold 
increase compared to baseline in 
total CCL17 at Days 7, 14, 28 
and 56 post-dose. 
To ensure that TE measures (% 
reduction in free CCL17, fold increase in 
total CCL17) are calculated at the same 
timepoints 
Objectives and 
Endpoints 
1.3 SOA 
Removal of COVID-19 SARS-
CoV-2 testing at Day 57, 113 and 
 and early withdrawal 
testing.    
IP is only administered once at the 
beginning of the study, and the 
remainder of the visits are data 
collection. Therefore, there is no reason 
to retest for COVID as withdrawal from 
the study will not occur based on a 
positive COVID test alone. 
1.3 SOA 
Addition of collection of smoking 
status information 
To aid understand impact of smoking on 
CCL17 levels 
1.3 SOA 
Update to footnotes 
Administration update  
1.3 SOA 
Extending visit window to  4 
days for visits on Day 141, 155 
and 
 
To aid with compliance to the study 
schedule 
2.3.1 Risk 
Assessment  
Deletion of ‘COVID-19 
Contingency Plan  
Any subject that presents with 
COVID-19-related symptoms 
and/or has a positive SARS-CoV-
2 PCR will be excluded from 
(further) participation in the trial 
and will receive follow-up medical 
attention as per local procedure’ 
Contradicts text in 7.2.3 – Covid stopping 
criteria  
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4.2 Scientific 
Rationale for 
Study Design 
 
Updated protocol reference  
Administration change 
5.1 Inclusion 
Criteria #7 
Geographical Ancestry criteria for 
Chinese participants update to 
include participants from Chinese 
Hong Kong or Taiwan 
To aid with participant recruitment 
5.1 Inclusion 
Criteria 
Requirements 
for Male 
Participants 
schematic 
Removal of ‘Requirement for 
Male Participants’ schematic 
Included in error. Decision tree is 
required for internal use only.  
6.3 Measures 
to Minimize 
Bias: 
Randomization 
and Blinding 
Removal of ‘(sponsor-open)’ in 
text of section  
This study is double blind and not 
sponsor-open. This was initially added in 
error so needed to be removed in this 
amendment.  
7.2.3 SARS-
CoV-2 related 
stopping 
criteria 
Removal of COVID stopping 
criteria 
This criterion is no longer necessary as a 
positive COVID test alone will not be 
reason for withdrawal from the study. 
COVID testing has been removed from 
the study, except testing prior to Day 1.  
 
 
 


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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ................................... 2 
TABLE OF CONTENTS .................................................................................................. 5 
1. 
PROTOCOL SUMMARY .......................................................................................... 8 
1.1. 
Synopsis ....................................................................................................... 8 
1.2. 
Schema ...................................................................................................... 12 
1.3. 
Schedule of Activities (SoA) ........................................................................ 13 
2. 
INTRODUCTION .................................................................................................... 18 
2.1. 
Study Rationale .......................................................................................... 18 
2.2. 
Background ................................................................................................ 18 
2.3. 
Benefit/Risk Assessment ............................................................................ 19 
2.3.1. 
Risk Assessment ......................................................................... 20 
2.3.2. 
Benefit Assessment ..................................................................... 28 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 28 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 29 
4. 
STUDY DESIGN .................................................................................................... 31 
4.1. 
Overall Design ............................................................................................ 31 
4.2. 
Scientific Rationale for Study Design .......................................................... 31 
4.3. 
 
4.4. 
End of Study Definition ............................................................................... 33 
5. 
STUDY POPULATION ........................................................................................... 34 
5.1. 
Inclusion Criteria ......................................................................................... 34 
5.2. 
Exclusion Criteria ........................................................................................ 36 
5.3. 
Lifestyle Considerations .............................................................................. 39 
5.3.1. 
COVID-19 related restrictions ...................................................... 39 
5.3.2. 
Meals and Dietary Restrictions .................................................... 39 
5.3.3. 
Caffeine, Alcohol, and Tobacco ................................................... 39 
5.3.4. 
Activity ......................................................................................... 39 
5.4. 
Screen Failures........................................................................................... 39 
6. 
STUDY INTERVENTION ........................................................................................ 41 
6.1. 
Study Intervention(s) Administered ............................................................. 41 
6.2. 
Preparation, Handling, Storage and Accountability ..................................... 42 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 43 
6.4. 
Study Intervention Compliance ................................................................... 44 
6.5. 
Continued Access to Study Intervention after the End of the Study ............ 44 
6.6. 
Treatment of Overdose ............................................................................... 44 
6.7. 
Concomitant Therapy.................................................................................. 45 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 45 
7.1. 
Discontinuation of Study Intervention .......................................................... 45 
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7.2. 
Study Stopping Criteria ............................................................................... 45 
7.2.1. 
Liver Chemistry Stopping Criteria ................................................ 46 
7.2.2. 
QTc Stopping Criteria .................................................................. 47 
7.2.3. 
SARS-CoV-2 related stopping criteria .......................................... 47 
7.3. 
Participant Discontinuation/Withdrawal from the Study ............................... 47 
7.4. 
Lost to Follow Up ........................................................................................ 48 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 48 
8.1. 
Efficacy and/or Immunogenicity Assessments ............................................ 49 
8.2. 
Safety Assessments ................................................................................... 49 
8.2.1. 
Physical Examinations ................................................................. 49 
8.2.2. 
Vital Signs .................................................................................... 49 
8.2.3. 
Electrocardiograms ...................................................................... 49 
8.2.4. 
Clinical Safety Laboratory Tests .................................................. 50 
8.2.5. 
Echocardiogram........................................................................... 50 
8.2.6. 
Skin Reactions ............................................................................. 50 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ......................................................................................... 51 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 51 
8.3.2. 
Method of Detecting AEs and SAEs ............................................. 51 
8.3.3. 
Follow-up of AEs and SAEs ......................................................... 52 
8.3.4. 
Regulatory Reporting Requirements for SAEs ............................. 52 
8.3.5. 
Pregnancy ................................................................................... 52 
8.4. 
Pharmacokinetics ....................................................................................... 53 
8.5. 
Target Engagement .................................................................................... 53 
8.6. 
Genetics ..................................................................................................... 54 
8.7. 
Biomarkers ................................................................................................. 54 
8.8. 
Immunogenicity Assessments ..................................................................... 54 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 55 
9.1. 
Statistical Hypotheses................................................................................. 55 
9.2. 
Analysis Sets .............................................................................................. 56 
9.2.1. 
Statistical Analyses ...................................................................... 57 
9.2.2. 
General Considerations ............................................................... 57 
9.2.3. 
Primary Endpoint(s) ..................................................................... 57 
9.2.4. 
Secondary Endpoint .................................................................... 57 
9.2.5. 
Exploratory Endpoint(s) ............................................................... 57 
9.2.6. 
Interim Analyses .......................................................................... 57 
9.3. 
Sample Size Determination ........................................................................ 58 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 59 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 59 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 59 
10.1.2. 
Financial Disclosure ..................................................................... 60 
10.1.3. 
Informed Consent Process .......................................................... 60 
10.1.4. 
Data Protection ............................................................................ 61 
10.1.5. 
Committees Structure .................................................................. 61 
10.1.6. 
Early Safety Data Review AND/OR Committee............................ 61 
10.1.7. 
Dissemination of Clinical Study Data ........................................... 61 


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10.1.8. 
Data Quality Assurance ............................................................... 62 
10.1.9. 
Source Documents ...................................................................... 63 
10.1.10. Publication Policy ......................................................................... 64 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 65 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 67 
10.3.1. 
Definition of AE ............................................................................ 67 
10.3.2. 
Definition of SAE .......................................................................... 68 
10.3.3. 
Recording and Follow-Up of AE and SAE .................................... 70 
10.3.4. 
Reporting of SAE to GSK ............................................................. 72 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ....................................... 73 
10.4.1. 
Definitions of Women of child bearing potential and 
Women of non-child bearing potential: ......................................... 73 
10.4.2. 
Contraception Guidance .............................................................. 74 
10.4.3. 
Collection of Pregnancy Information: ........................................... 75 
10.5. 
Appendix 5: Genetics .................................................................................. 76 
10.6. 
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments .............................................................................................. 77 
10.7. 
Appendix 7: Abbreviations and Definitions and Trademarks ....................... 79 
10.8. 
Amendment History .................................................................................... 81 
11. REFERENCES ....................................................................................................... 85 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title:  
A Randomised, Double-blind, Placebo-controlled Study of the Safety, Tolerability, 
Pharmacokinetics, Target Engagement and Immunogenicity of a single subcutaneous 
dose of GSK3858279 administered to Healthy Caucasian, Chinese and Japanese 
Participants 
Brief Title:  
Safety, tolerability, pharmacokinetics and target engagement of GSK3858279 after a 
single subcutaneous dose in healthy Caucasian, Chinese and Japanese participants.   
Rationale: 
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), 
target engagement (TE) and immunogenicity of a single subcutaneous (SC) dose of 
GSK3858279 when administered to healthy Caucasian, Chinese and Japanese 
participants. 
This study will facilitate inter-ethnic comparisons while minimising variations rendered 
by cross-study assessments. 
The outcomes of this study are intended to support the inclusion of Chinese and Japanese 
participants in global Ph2/3 studies. 
Objectives and Endpoints  
Objectives 
Endpoints 
• 
Primary 
 
• 
To 
evaluate 
the 
safety 
and 
tolerability of a single SC dose of 
GSK3858279 compared with placebo 
administered 
to 
healthy 
participants 
including cohorts of Japanese, Chinese and 
Caucasians 
• 
Incidence of adverse events (AEs), 
serious adverse events (SAEs), 
withdrawals due to AEs 
• 
Occurrence of clinically important 
changes from baseline in clinical 
laboratory parameters (haematology, 
clinical chemistry, urinalysis), vital 
signs (blood pressure, heart rate, body 
temperature), and cardiac parameters 
(electrocardiogram)  
• 
To assess the pharmacokinetic 
(serum PK) profile up to 56 days following 
a single SC dose of GSK3858279 in 
• 
PK parameters: area under the 
concentration-time curve (AUC(0-
56), AUC(0-t) post-dose), time of 


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Objectives 
Endpoints 
healthy participants including cohorts of 
Japanese, Chinese and Caucasians 
occurrence of last quantifiable 
concentration (tlast), maximum 
observed concentration (Cmax), and 
time of occurrence of Cmax (tmax) 
per cohort as data permits 
• 
Secondary 
 
• To evaluate target engagement (TE) 
up to 56 days following a single SC 
dose of GSK3858279 in healthy 
participants including cohorts of 
Japanese, Chinese and Caucasians.  
• Reduction (%) from baseline in free 
CCL17: maximum, minimum and at 
Days 7, 14, 28 and 56, post-dose 
• Total CCL17 (free and when bound to 
GSK3858279): maximum observed 
concentration (Cmax), time of Cmax 
(tmax), maximum fold increase 
compared to baseline, fold increase 
compared to baseline at Days 7, 14, 28 
and 56, post-dose.  
• To assess the potential for anti-drug 
antibody (ADA) formation 
• Incidence of pre-existing ADAs 
• Incidence of treatment-emergent ADAs 
over time (and whether neutralising) 
• 
Exploratory 
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Objectives 
Endpoints 
 
Overall Design: 
This is a randomised, double-blind, placebo-controlled, study with a single SC dose of 
GSK3858279 administered to healthy Caucasian, Chinese and Japanese participants.  
 
To try to eliminate any time dependant variability among ethnic groups, we will aim to 
treat Caucasian and Asian groups concurrently.  
 
Participants will attend a screening visit at the clinical units within 28 days of Study Day 
1. If eligible for the study, participants will return on Day -1 and maybe admitted to the 
unit overnight for final screening checks in preparation for randomization and dosing 
(Day 1).  Participants will remain at the clinical units until Day 3. 
 
• 
All participants will remain in the study until at least 
  It 
will be mandatory for the Caucasian cohort to continue 
. The extended follow-
up period 
) is to better understand the apparent non complete 
return of free CCL17 to baseline values as observed in Part A of Study 207804 across all 
dose groups. 
 (primary 
endpoints defined from data up to and including Day 57).  Safety information will be 
collected throughout the study.    
• 
Study intervention will be administered as four separate SC injections of either 
GSK3858279 
) or placebo in a 7:3 ratio, respectively for each cohort. 
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Study Population 
Although reproductive toxicity studies have not yet been conducted, both males and 
females (of non-reproductive potential) are permitted under the conditions specified (see 
Inclusion Criteria). 
Healthy participants have been chosen because: 
• 
Comorbidities and concomitant medications of patient participants may confound 
analysis. 
• 
Patient participants (e.g. osteoarthritis) will derive little or no benefit from a single 
dose of GSK3858279, and their participation in this study would preclude treatment 
with accessible efficacious therapies. 
Number of Participants: 
Approximately 10 participants are to be randomized (7 active: 3 placebo) per cohort 
aiming to achieve at least 6 evaluable participants on active and 2 on placebo per cohort. 
An evaluable participant is one that has been dosed and has safety and all PK data up to 
Day 57. 
Replacements (assigned to the same treatment) are permitted at the discretion of the 
sponsor in consultation with the investigator. For example, in the event of a participant 
withdrawing before Day 57 the participant will be replaced.   
Note: Enrolled means a participant's, or their legally acceptable representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process and screening. 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, unless otherwise specified by the protocol. 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: 
Three cohorts of approximately 10 participants in each cohort (Caucasian, Chinese and 
Japanese) will be randomized to a single dose of 
 SC GSK3858279 or placebo 
(7:3 ratio) (Appendix 1). 
• Approximately 10 eligible participants per cohort will be admitted to the 
clinical unit on the day prior to dosing (Day-1). On Day 1, each participant 
will receive a SC dose of GSK3858279 or placebo, administered as four 
separate SC injections, in a 7:3 ratio, respectively. 
• Participants will then remain as an in-patient until discharged on Day 3 after 
assessments have been performed. 
• Participants will then return to the clinical unit for outpatient visits as 
described in the SoA. 
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• The final required follow up visit will be at the clinical unit on 
 for 
Chinese and Japanese participants. NB: Japanese and Chinese participants 
have an option to remain in the study 
. 
• The final follow up visit will be at the clinical unit on 
 for Caucasian 
participants. 
• The maximum dose will not exceed 
 SC. 
 
The study duration is not expected to exceed a maximum of 
: (Screening 
[up to 28 days] and a follow-up period of up to 
. Follow-up may be extended 
if a serious or clinically significant AE has not resolved by 
. 
 
Data Monitoring/ Other Committee:  
No blinded Safety Review Team (uSRT) 
 
 
 
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1.3. 
Schedule of Activities (SoA) 
Screening period  
Procedure 
Screening  
(Day -28 to Day -1) 
Informed consent 
X 
Inclusion and exclusion criteria 
X 
Demography 
X 
Full Physical examination including height and weight 
X 
Medical/medication/drug/alcohol history1   
X 
Alcohol & Tobacco screens2 
X 
Urine drug screen 
X 
FSH (in WONCBP) 
X 
HIV, Hepatitis B and C screening 
X 
Haematology, clinical chemistry, urinalysis  
X 
COVID-19 (SARS-CoV-2) PCR or rapid antigen test 
X 
TB screening (QuantiFERON) 
X 
12-lead ECG3 
X 
Vital signs4 
X 
Echocardiogram 
X 
AE assessment 
X 
SAE assessment 
X 
Target Engagement Sample Collection  
X 
1. To include substance usage, family history of premature cardiovascular disease, medication, 
drug/alcohol history 
2. As per local standard practice 
3. Performed in triplicate 
4. Vital signs are to be taken before blood collection for laboratory tests 


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Treatment and Follow-up 
Procedure  
  
  
Treatment and Follow-up (FU)  
Week  
  
1 
2 
3 
4 
EW1  
 Day  
-2 
-1 
1a 
2 a 
3a 
5b 
8b 
15b 
22b 
29b 
  
Outpatient visit  
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Inpatient Stay  
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge from 
clinical unit  
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and 
exclusion criteria  
 
 
X2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brief Physical 
examination  
 
 
X3 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
X 
Alcohol & 
Tobacco screens  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine drug screen  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
(triplicate)  
 
X 
X4 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs  
 
X 
X5 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Smoking Status 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Procedure  
  
  
Treatment and Follow-up (FU)  
Week  
  
1 
2 
3 
4 
EW1  
 Day  
-2 
-1 
1a 
2 a 
3a 
5b 
8b 
15b 
22b 
29b 
  
Haematology, 
clinical chemistry, 
urinalysis  
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X6 
X 
X 
X 
X 
X 
X 
COVID-19 SARS-
CoV-2 PCR or 
rapid antigen test   
X7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dosing (SC) 
injections  
 
 
X8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK & TE  
X9 
 
X10 
X10 
X10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity  
 
 
X11 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
 
X 
X 
PD serum/plasma 
samples (For 
protein 
biomarkers)  
 
 
X 
 
X 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
X 
PD WB PAXgene 
samples (For 
transcriptomic 
analyses)  
 
 
X 
 
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
X 
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Procedure  
  
  
Treatment and Follow-up (FU)  
Week  
  
1 
2 
3 
4 
EW1  
 Day  
-2 
-1 
1a 
2 a 
3a 
5b 
8b 
15b 
22b 
29b 
  
PGx  
 
 
X12 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAE and AE  
(SAEs recorded 
throughout. AEs 
recorded from first 
SC injection) 
<-------------------------------------------------------------------------------------------->  
X  
Concomitant meds  
<-------------------------------------------------------------------------------------------->  
X  
AE= adverse event; ECG= Electrocardiogram, SC = subcutaneous; PD = pharmacodynamics, PK= 
pharmacokinetics; SAE= serious adverse event, TE = Target engagement  
* Visits optional for Chinese and Japanese participants  
a ± 2hrs  
b ± 1 day 
c ± 4 day 
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1 Early withdrawal 
2 Re-check clinical status before dose of study medication  
3 Prior to dosing  
4 pre-dose and 60 mins post start of SC injections  
5 pre-dose, 30 mins, 1h, 2h, 3h & 4 h post start of SC injections  
6 NT-pro BNP. NB: Troponin I at all time points  
7 Result to be available prior to dose of study drug. Day -2 for PCR or rapid antigen test  
8 Study intervention administered as 4 separate injections 
9 Only TE sample 
10 PK and TE blood samples taken pre-dose, 6h, 12h, 24h, 36h and 48h post start of SC injections, respectively 
11 Blood sample to be taken pre-dose 
12 Taken pre-dose 
 
• 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 
2.1. 
Study Rationale 
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), 
target engagement (TE) and immunogenicity of a single subcutaneous (SC) dose of 
GSK3858279 when administered to healthy Caucasian, Chinese and Japanese 
participants.  
The outcomes of this study are intended to support the inclusion of Chinese and Japanese 
participants in global Ph2/3 studies. 
2.2. 
Background 
CCL17, previously known as thymus and activation regulated chemokine (TARC), is a 
member of the CC-family of chemokines that binds and signals through the G-protein 
coupled CC-chemokine receptor, CCR4 [Imai, 1996; Imai, 1997]. CCL17 is produced by 
numerous immune and non-immune cell types. CCR4 is predominantly expressed on Th2 
cells but is also present on other immune and non-immune cell types. 
, monoclonal antibody (mAb), binding specifically to the 
chemokine CCL17. It functionally inhibits CCL17 activating the chemokine receptor 
CCR4, to prevent downstream consequences of CCR4 signalling. 
At the time of this protocol, GSK3858279 is being developed for treatment of 
osteoarthritis pain. Alleviating chronic pain is a major unmet need, as current therapies 
(e.g. NSAIDs, opioids) have significant side effects and addiction liabilities that prevent 
their effective use in treating the patient's pain. 
Rationale for CCL17 neutralisation in OA pain has been generated in vivo pre-clinically 
and inflammatory and arthritis models. CCL17 has been recently identified as a 
peripheral mediator of inflammatory pain and can itself induce arthritis.  
In light of the global COVID-19 pandemic, all participants will be screened for COVID-
19 at the beginning of the study and will be required to have a negative SARS-Cov-2 test 
prior to commencing the study. All participants will also be required to show evidence of 
complete COVID vaccination to be eligible to participate in the study.  Please see further 
details for risk assessment and mitigation strategy below. 
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2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events (AEs) of GSK3858279 may be found in the see 
Investigator’s Brochure 
 Effective 02 JUL 2021. 
Details of these risks, as well as the risks associated with the procedures, and the 
proposed strategy to mitigate/monitor these risks are detailed in Section 2.3.1. 
In this study, safety will be monitored closely both by subjective reporting and by 
objective means, i.e. serial assessments of vital signs, clinical laboratory information and 
cardiac monitoring. The study will be run in a clinical unit with access to hospital 
facilities for the treatment of medical emergencies. Participants will remain monitored in 
the clinic for a minimum of 2 hours after completion of dosing but will remain in the 
clinic until Day 3 and will only be discharged from the unit if the investigator deems it 
safe to do so. 
 
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2.3.1. 
Risk Assessment 
Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
Investigational Product (IP)  
Hypersensitivity, 
including injection 
site and infusion 
reactions 
The administration of any (human) mAb has the potential to induce local or 
systemic immunologic reactions, for example acute allergic reactions (type I) 
and immune complex disease (ICD) associated with the formation of anti-
drug antibodies (ADA) (type III). 
 
Participant Selection: 
Participants with a history of sensitivity to the 
study medication, or a history of any drug or 
other allergy that, in the opinion of the 
investigator, contraindicates their participation, 
will not be permitted to enter the study. 
Participants with renal disorders will also be 
excluded. 
  
Participant monitoring: 
In Part A of FiH study (207804), participants 
remained in the inpatient facility for 48 hours 
post dosing to allow adequate monitoring by 
trained site personnel.  
In Part B of FiH (207804) and in this study 
(212979), participants will be monitored for a 
minimum of two hours post dosing. 
Emergency resuscitation facilities will also be 
available. 
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Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
Participants will be instructed in the Informed 
Consent Form (ICF) as to the signs and 
symptoms of hypersensitivity reactions and be 
instructed to seek immediate clinical care 
should they develop.  
 
Immunogenicity 
Samples will be drawn at baseline and at 
regular intervals to test for immunogenicity, and 
participants will be monitored for any evidence 
of adverse reaction as detailed in the 
hypersensitivity section of this table. 
Clinical laboratory safety assessments are 
included in the study. Urine microscopy and 
laboratory quantification of proteinuria will be 
investigated following unexplained dipstick 
proteinuria or haematuria. 
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Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
Risk of Infection 
The intended pharmacologic effect of GSK3858279 may result in an 
 
. 
Participant Selection 
Participants with active or chronic infections or a 
history of recent or recurrent infections will not 
be included in the study – see Section 5.1. 
 
Participant Monitoring 
Participants will be monitored for infection. 
Participants will be instructed in the ICF as to 
the signs and symptoms of infection, and to 
contact the site personnel should they develop. 
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Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
Vaccination 
Reactions 
Participant selection and non-permitted 
medications: 
Attenuated live vaccines should not be 
administered to participants within 30 days prior 
to dosing and for five half-lives after dosing. If 
indicated, non-live vaccines (e.g. inactivated 
influenza vaccines) may be administered whilst 
receiving GSK3858279 based on an 
assessment of the benefit:risk (e.g. risk of 
decreased responsiveness). 
Cardiac Risks 
Participant Exclusion: 
Participants with a history of cardiac disease or 
cardiac abnormalities (including abnormal 
Troponin I and NT-proBNP) that, in the opinion 
of the investigator, would compromise cardiac 
safety will be excluded from the study.  
Participant monitoring: 
Investigations during screening include ECG, 
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Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
echocardiogram and troponin I and NT-proBNP. 
Troponin I and NT-proBNP will be monitored 
after dosing.  
Bleeding Risk 
Participant exclusion and non-permitted 
medication 
Participants with a previous or current history of 
bleeding diathesis will be excluded. 
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Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
Use of anti-coagulants or anti-platelet agents 
will be prohibited. 
Skin Reactions 
Participant Exclusion 
Participants with a history of drug-induced skin 
reactions and Stevens-Johnson Syndrome will 
be excluded. 
 
Participant Monitoring 
Clinically significant skin reactions will be 
reviewed by a dermatologist and, if appropriate, 
a skin biopsy will be requested for histological 
analysis. 
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Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
Clinical 
There were no reports of any clinically significant skin reactions during Part 
A of the FiH study (207804) in healthy participants. 
Study Procedures 
Risk associated 
with blood 
draws 
Fainting, mild pain, bruising, irritation or redness at phlebotomy site, may be 
associated with blood draws.   
Experienced site staff will follow standard 
approaches for managing events related to 
blood draws 
Other 
SARS-CoV-2 
The current SARS-CoV-2 pandemic can pose a challenge to integrity of the 
trials, protection of participants’ rights, safety and wellbeing and the safety of 
clinical trial staff. Therefore, risk mitigation strategies will be put in place for 
this trial and will be evaluated on an ongoing basis for the duration of this 
trial, or until there is a consensus that the period of the SARS-CoV-2 
outbreak in the Australia has passed. If the dynamics of the SARS-CoV-2 
outbreak change in such a way that the safety of the trial participants and 
clinical trial staff or integrity of the data collected during this clinical trial 
cannot be guaranteed, the trial will be halted. 
 
Participant selection and monitoring 
Healthy subjects in the current study fall in a low 
risk category for complications of COVID-19, the 
disease caused by the SARS-CoV-2 virus. To 
reduce the risk of SARS-CoV-2 infections 
among trial participants, measures and 
procedures based on the advice issued by GSK 
Global COVID Guidance should be followed. 
These would include but are not limited to 
counselling participants regarding the 
importance of infection control measures such 
as hand washing, reducing inter-personal 
contacts as much as possible and participant 
awareness of potential COVID-19 symptoms. 
 
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Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
Participants must also show evidence of 
complete COVID-19 vaccination to be eligible to 
participate in the study 
 
Site trial staff in direct contact may receive 
additional protection via the use of Personal 
Protective Equipment (PPE) and disinfectants 
as per local guidance.  
All trial subjects will be screened for SARS-
CoV-2 with a PCR or lateral flow test:  
1) at initial screening 
2) prior to admission to the clinical unit and  
3) in case of symptoms possibly related to 
COVID-19   
 
Protection of Trial Integrity 
Adherence to the protocol protects the integrity 
of the data collected during this clinical trial, as 
well as participants’ data protection rights. 
 
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2.3.2. 
Benefit Assessment 
There will be no direct benefit to the healthy participants in this study.  However, 
participants will undergo a medical evaluation during screening (including physical 
examination, electrocardiogram (ECG), vital signs and laboratory assessments), which 
may provide important health information The information obtained in this study will 
inform the conduct of future clinical studies to contribute to the process of developing 
new therapies for diseases such as Osteoarthritis where there is high unmet medical need. 
 
2.3.3. 
Overall Benefit: Risk Conclusion 
The safety of each individual participant has been prioritised and the eligibility, 
monitoring, enhanced monitoring and study level stopping criteria described in Section 7 
have been designed to minimise risks to participants associated with exposure to 
GSK3858279. However, participants will undergo a medical evaluation during screening 
(including physical examination, electrocardiogram (ECG), vital signs and laboratory 
assessments), which may provide important health information. Taking into account these 
measures designed to minimise risks, the potential risks identified in association with 
GSK3858279 are justified.   


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3. 
OBJECTIVES AND ENDPOINTS  
Objectives 
Endpoints 
Primary 
• 
To evaluate the safety and 
tolerability of a single SC dose of 
GSK3858279 
compared 
with 
placebo administered to healthy 
participants including cohorts of 
Japanese, Chinese and Caucasians 
• 
Incidence of adverse events (AEs), 
serious adverse events (SAEs), 
withdrawals due to AEs 
• Occurrence of clinically important 
changes from baseline in clinical 
laboratory parameters (haematology, 
clinical chemistry, urinalysis), vital signs 
(blood pressure, heart rate, body 
temperature), and cardiac parameters 
(electrocardiogram)  
• 
To assess the 
pharmacokinetic (serum PK) profile 
up to 56 days following a single SC 
dose of GSK3858279 in healthy 
participants including cohorts of 
Japanese, Chinese and Caucasians 
• PK parameters: area under the 
concentration-time curve (AUC(0-56), 
AUC(0-t) post-dose), time of occurrence 
of last quantifiable concentration (tlast), 
maximum observed concentration 
(Cmax), and time of occurrence of Cmax 
(tmax) per cohort as data permits 
Secondary 
• To evaluate target engagement 
(TE) up to 56 days following a 
single SC dose of GSK3858279 
in healthy participants including 
cohorts of Japanese, Chinese and 
Caucasians.  
• Reduction (%) from baseline in free 
CCL17: maximum, minimum and at 
Days 7, 14, 28 and 56, post-dose 
• Total CCL17 (free and when bound to 
GSK3858279): maximum observed 
concentration (Cmax), time of Cmax 
(tmax), maximum fold increase 
compared to baseline, fold increase 
compared to baseline at Days 7, 14, 
28 and 56, post-dose.  
 
• To assess the potential for anti-
drug antibody (ADA) formation 
• Incidence of pre-existing ADAs 
• Incidence of treatment-emergent ADAs 
over time (and whether neutralising) 
Exploratory 
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Objectives 
Endpoints 
 
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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a randomised, double-blind, placebo-controlled, multi-centre study with a single 
SC dose of GSK3858279 administered to healthy Caucasian, Chinese and Japanese 
participants. 
 
• Participants will attend a screening visit at the clinical units within 28 days of Study 
Day 1. If eligible for the study, participants will return on Day -1 and will be admitted 
to the unit overnight for final screening checks in preparation for randomization and 
dosing (Day 1). 
• Participants will be randomized to either GSK3858279 or placebo in a ratio of 7:3 per 
cohort. 
• Each participant will receive a 
 SC dose of GSK3858279 or placebo, 
administered as four separate SC injections. 
• Participants will then remain as an inpatient until discharged on Day 3 after 
assessments have been performed. 
• Participants will then return to the clinical unit for outpatient visits as described in the 
SoA. 
• It will be mandatory for the Caucasian cohort to continue 
, where 
they will have their final follow up visit at the clinical unit.  The final required 
follow up visit will be at the clinical unit on 
 for Chinese and 
Japanese participants. NB: Japanese and Chinese participants have an option 
to remain in the study until 
 
• The maximum dose will not exceed 
 SC 
 
4.2. 
Scientific Rationale for Study Design 
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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. 
A participant is considered to have completed the primary endpoint if he or she has 
completed the treatment and day 57. 
A participant is considered to have completed the study if he or she has completed the 
treatment and follow-up phases of the study including the last scheduled procedure 
shown in the SoA. 
 
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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment 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: 
TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS 
1. Participants who are overtly healthy as determined by medical evaluation including 
medical history, physical examination, laboratory tests and cardiac monitoring [12-
lead ECGs].   
A participant with a clinical abnormality or laboratory parameter(s) outside of the 
reference range for the population being studied that is not specifically listed in the 
inclusion or exclusion criteria may be included if the Investigator (in consultation 
with the GSK Medical Monitor if required) agrees and documents that the finding 
is unlikely to introduce additional risk factors and will not interfere with the study 
procedures or interpretation. 
AGE 
2. Between 20 and 65 years of age inclusive, at the time of signing the informed 
consent.  
INFORMED CONSENT 
3. Capable of giving signed informed consent which includes compliance with the 
requirements and restrictions listed in the informed consent form (ICF) and in this 
protocol. 
COVID-19 (SARS CoV-2) Vaccination 
4. Participants who have evidence of completed vaccination for SARS-CoV-2 
with an approved vaccine  
WEIGHT  
5. Body weight within the range 45 – 100 kg and body mass index (BMI) 
within the range 18-29.9 kg/m2 (inclusive) for Chinese and Japanese 
participants.  Caucasian participants must exhibit BMI range of 18 – 32.0 
kg/m2 . 
GEOGRAPHICAL ANCESTRY 
6. Japanese Participants are eligible based on meeting all of the following: 
• Participants born in Japan 
• Descendants of four ethnic Japanese grandparents and two ethnic Japanese 
parents 
• Have lived outside Japan for less than 10 years at the time of screening 
7. Chinese Participants are eligible based on meeting all of the following: 


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• Participant born in mainland China, Hong Kong or Taiwan  
• Descendants of four ethnic Chinese grandparents and two ethnic Chinese 
parents 
• Have lived outside mainland China, Hong Kong or Taiwan for less than 10 
years at the time of screening 
8. Caucasian Participants are eligible based on meeting the following:  
• Declaration of familial Caucasian/European ancestry (having 2 parents of 
Caucasian/European ancestry and 4 grandparents of Caucasian/European 
ancestry) 
SEX   
9. Male or female participant: 
a. Male participants: 
Male participants are eligible to participate if they agree to the following for at least 
28 weeks after the dose of study intervention:  
• Refrain from donating sperm 
PLUS either: 
• Be abstinent from heterosexual intercourse as their preferred and usual 
lifestyle (abstinent on a long term and persistent basis) and agree to remain 
abstinent  
OR 
• Must agree to use contraception/barrier as detailed below  
o Agree to use a male condom  
o and should also be advised of the benefit for a female partner to use 
a highly effective method of contraception (see Section 10.4) as a 
condom may break or leak when having sexual intercourse with a 
woman of childbearing potential who is not currently pregnant 
b. Female participants:  
A female participant is eligible to participate if she is of non-reproductive potential as 
defined in Section 10.4. 
. 
 
 


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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
MEDICAL CONDITIONS 
1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, 
endocrine, haematological, 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.  
2. Personal or family history of cardiomyopathy. 
3. Abnormal blood pressure at screening as determined by the investigator. 
4. History of symptomatic herpes zoster  
5. Evidence of active or latent tuberculosis (TB) as documented by medical history, 
examination, and TB testing with a positive (not indeterminate) QuantiFERON 
test. 
NOTE: In cases where the QuantiFERON test is indeterminate, the participant may 
have the test repeated once, but they will not be eligible for the study unless the second 
test is negative. In cases where the QuantiFERON test is positive, the participant 
should be followed up as per standard of care. If a locally-read follow up chest x-ray 
shows no evidence of current or previous pulmonary tuberculosis, the participant may 
be eligible for the study at the discretion of the Investigator and GSK Medical Monitor. 
6. Significant allergies to humanized monoclonal antibodies as per principal 
investigator’s and GSK medical monitor’s judgements.  
7. History or evidence of 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 (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative 
dermatitis) 
8. History of lymphoma, leukaemia, or any malignancy within the last 5 years except 
for basal cell or squamous epithelial carcinomas of the skin that have been 
resected with no evidence of metastatic disease for 3 years. 
9. Alanine transaminase (ALT) >1.5x upper limit of normal (ULN)  
10. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%).  
11. Current or chronic history of liver disease, or known hepatic or biliary 
abnormalities (with the exception of Gilbert's syndrome or asymptomatic 
gallstones) 
12. Corrected QT (QTc) >450 msec  
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• 
The QTc is the QT interval corrected for heart rate according to Bazett’s 
formula (QTcB), Fridericia’s formula (QTcF), and/or another method, 
machine-read or manually over-read. 
• 
The specific formula that will be used to determine eligibility and 
discontinuation for an individual participant should be determined prior to 
initiation of the study. In other words, several different formulae cannot be 
used to calculate the QTc for an individual participant and then the lowest 
QTc value used to include or discontinue the participant from the trial. 
• 
For purposes of data analysis, QTcF, another QT correction formula, or a 
composite of available values of QTc will be used as specified in the 
Reporting and Analysis Plan (RAP). 
13. History of Stevens Johnson Syndrome 
14. Known immunodeficiency 
15. Participants with a chronic infection (e.g., osteomyelitis), who have been receiving 
treatment within three months prior to dosing or individuals with an active 
infection. 
16. Previous or current history of bleeding diathesis, excessive bleeding or coagulation 
disorders 
17. History of significant medical illness in the opinion of the investigator would  
interfere with the study procedures and / or assessments 
 
PRIOR/CONCOMITANT THERAPY 
18. Intended use of over-the-counter or prescription medication including herbal  
medications within 7 days prior to dosing  (or 14 days if the drug is a potential 
enzyme inducer) or 5 half-lives (whichever is longer) before the start of study 
intervention until completion of the follow-up visit, unless, in the opinion of the 
investigator and sponsor, the medication will not interfere with the study.  
19. Live vaccine(s) or plans to receive such vaccines within 1 month of screening until  
final follow-up visit. 
20. Treatment with biologic agents (such as monoclonal antibodies including 
marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to 
dosing 
21. Treatment with antiplatelet or anticoagulant agents within 7 days of dosing 
22. Major surgery (as per investigator’s judgement) within 3 months prior to dosing 
 
PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE 
23. Participation in the study would result in loss of blood or blood products in excess  
of 500 mL within 3 months. 


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24. Exposure to more than 4 new chemical entities within 12 months prior to the first  
dosing day. 
25. Current enrolment or past participation in any other clinical study involving an  
investigational drug intervention within the last 3 months or 5 half-lives 
(whichever is longer) of signing the ICF 
 
DIAGNOSTIC ASSESSMENTS 
26. Presence of Hepatitis B surface antigen (HBsAg) at screening. 
27. Presence of the Hepatitis B core antibody (HBcAb) at screening. 
28. Positive Hepatitis C antibody test result at screening. 
NOTE: Participants with positive Hepatitis C antibody due to prior resolved 
disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is  
obtained 
29. Positive Hepatitis C RNA test result at screening or within 3 months prior to first 
dose of study intervention 
NOTE: Test is optional and participants with negative Hepatitis C antibody test 
are not required to also undergo Hepatitis C RNA testing. 
30.  Abnormal clinically significant echocardiogram at screening, as assessed by the 
investigator. 
31. Cardiac troponin or NT-proBNP levels out of normal range at screening. 
32. Positive pre-study drug/alcohol screen 
33. Positive human immunodeficiency virus (HIV) antibody test 
34. Positive coronavirus (COVID-19): SARS-CoV2 PCR or lateral flow test of a 
combined throat and nasopharyngeal swab or nasal swab only 
 
OTHER EXCLUSIONS 
35. Regular alcohol consumption within 6 months prior to the study defined as:  
• 
an average weekly intake of >11 standard drinks for males and females. One 
standard drink contains 10g of alcohol.  
36. Regular use of known drugs of abuse.  
37. Sensitivity to any of the study interventions, or components thereof, or drug or 
other allergy that, in the opinion of the investigator or medical monitor, 
contraindicates participation in the study. 
 


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5.3. 
Lifestyle Considerations 
5.3.1. 
COVID-19 related restrictions 
Participants will be required to adhere to the measures and procedures outlined in the 
hospital policy, based on the advice issued by the State health minister and COVID-19 
measures declared by the Australian  government, to reduce risk of SARS-CoV-2 
infections among trial participants and clinical site staff. 
5.3.2. 
Meals and Dietary Restrictions 
Not Applicable. 
5.3.3. 
Caffeine, Alcohol, and Tobacco 
• Participants will not be allowed to have excessive caffeine consumption, defined as 
>800 mg per day from 7 days prior to the first dose of the study drug until 24 hours 
prior to dosing. Participants will abstain from caffeine-containing products for 24 
hours prior to each visit to the study unit. Caffeine quantities defined as: one cup of 
coffee contains 100 mg of caffeine; one cup of tea, or one glass of cola, or portion of 
chocolate (dark: 100 g, milk: 200 g) contains approximately 40 mg of caffeine; one 
250 ml can of Red Bull contains approximately 80 mg of caffeine. 
• Alcohol will not be allowed from at least 24 hours before each scheduled visit, and 
whilst in the study unit until discharge from the study unit. At other times throughout 
the study, participants should not consume more 1.5 standard drinks of alcohol daily 
on average (10g alcohol in 1 Australian standard drink). Participants may undergo an 
alcohol breath test at the discretion of the investigator.  
• Non-smokers or light smokers (<= 5 cigarettes / nicotine-forms per week) may be 
enrolled in the trial.  Light smokers must abstain from nicotine-containing products 
for at least 3 days prior to Day 1 dosing and for the duration of the inpatient stay. 
 
5.3.4. 
Activity 
• Participants will abstain from strenuous exercise for 48 hours before each blood 
collection for clinical laboratory tests. Participants may participate in light 
recreational activities during studies (e.g., watching television, reading). 
 
5.4. 
Screen Failures 
A screen failure occurs when a participant who consents to participate in the clinical 
study is not subsequently randomized/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 (CONSORT) 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, any protocol 
deviations and any serious adverse events (SAEs). 


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Repeat assessments during the screening period: Assessments, including laboratory 
assessments, may be repeated once if determined necessary by the investigator, for 
example: (a) in cases of technical malfunction (e.g. loss of laboratory specimen), (b) in 
the event of a value close enough to the exclusionary threshold that it may reasonably lie 
within the degree of variability of the assay or an indeterminate result; (c) if there is 
reason to believe the result may be false (i.e. contradicts recent result for the same 
parameter). These are repeat assessments and not rescreening events. If the original result 
was exclusionary and is confirmed by repeat testing, the participant will be excluded 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened once, unless a positive SARS-Cov-2 test results is obtained where re-
screening is not permitted. Rescreened participants should be assigned a new participant 
number. 


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6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Study Intervention(s) Administered 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol 
 
Table 1 
Study Interventions Administered 
ARM Name 
Active 
Placebo 
Intervention Name 
GSK3858279 
Placebo 
Type  
 
Placebo 
Dose Formulation  
Solution for injection. 
 
 
Unit Dose Strength 
 
 
 
 
 
Dosage Levels 
 
Single dose 
Route of 
Administration 
SC injection 
SC injection 
Dosing Instructions 
Use 
Experimental 
Placebo-control 
IMP and NIMP 
IMP 
Placebo 
Sourcing 
 
Study medication is supplied by GSK. 
Provided locally by the trial 
site, subsidiary, or designee. 
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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Packaging and 
Labelling 
 
Bulk supplies will be provided in a vial 
contained within a carton. Each vial 
and carton will be labelled as required 
per country requirement. Dispensed 
medication will be labelled as required 
per country requirement. 
Commercial presentation. 
Dispensed placebo will be 
labelled as required per 
country requirement. 
 
 
 
 
 
 
.   
 
6.2. 
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). 
• Further guidance and information for the final disposition of unused study 
intervention are provided in the SRM.  
• Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff.  Take adequate precautions to 
avoid direct eye or skin contact and the generation of aerosols or mists. In the case of 
unintentional occupational exposure notify the monitor, Medical Monitor and/or GSK 
study contact. 
• A Material Safety Data Sheet (MSDS)/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 
GSK. 
CCI
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Precaution will be taken to avoid direct contact with the study intervention.  A Material 
Safety Data Sheet (MSDS) describing occupational hazards and recommended handling 
precautions will be provided to the investigator. In the case of unintentional occupational 
exposure notify the monitor, Medical Monitor and/or GSK study contact. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Participants who meet the screening eligibility criteria will be randomised to a treatment 
group through the Interactive Web Response System (IWRS). Before the study is 
initiated, the log in information and directions for the IWRS will be provided to the site. 
 
Once assigned, a randomisation number must not be reassigned to another participant in 
the study. This will be a double blind study with both the investigator and participant 
blinded to study treatment. Site personnel will remain blinded. There will, however, be an 
unblinded site pharmacy personnel to prepare the study intervention; but they will not 
have contact with study participants  
The following will apply: 
• The IWRS will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding 
of a participants’ intervention assignment is warranted. Participant safety must always 
be the first consideration in making such a determination. 
• If the investigator decides that unblinding is warranted, the investigator should make 
every effort to contact GSK prior to unblinding a participant’s intervention 
assignment unless this could delay emergency intervention of the participant. If a 
participant’s intervention assignment is unblinded, GSK must be notified within 24 
hours after breaking the blind. 
• The date and reason that the blind was broken must be recorded in the source 
documentation and case report form, as applicable. 
• GSK’s Safety and Medical Governance (SMG) staff may unblind the intervention 
assignment for any participant with an SAE. If the SAE requires that an expedited 
regulatory report be sent to one or more regulatory agencies, a copy of the report, 
identifying the participant’s intervention assignment, may be sent to investigators in 
accordance with local regulations and/or GSK policy. 
• Sites will be required to make every effort to ensure that the results of study 
laboratory tests are not proactively communicated to participants during the study 
unless essential for clinical care.   
 
GSK3858279 PK and Free and Total CCL17 results that may unblind the study will not 
be reported to investigative sites or blinded personnel until the study has been unblinded. 
A participant will be withdrawn if the participant’s intervention code is unblinded by 
the investigator or treating physician. The primary reason for discontinuation (the 
event or condition which led to the unblinding) will be recorded in the CRF. The 
participant will be followed up for safety monitoring if treatment was received 
 


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GSK’s Safety Evaluation and Risk Management (SERM) staff may unblind the 
intervention assignment for any participant with an SAE. If the SAE requires that an 
expedited regulatory report be sent to one or more regulatory agencies, a copy of the 
report, identifying the participant’s intervention assignment, may be sent to investigators 
in accordance with local regulations and/or GSK policy. 
6.4. 
Study Intervention Compliance 
• 
When participants are dosed at the site, they will receive study intervention directly 
from the investigator or designee, under medical supervision. The date and time of 
each dose administered in the clinic will be recorded in the source documents. The 
dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering 
the study intervention.   
 
6.5. 
Continued Access to Study Intervention after the End of the 
Study 
This is a single dose study in healthy participants. No study intervention will be provided 
following the end of the study. 
 
6.6. 
Treatment of Overdose 
For this study, any dose of GSK3858279 greater than the scheduled dose will be 
considered an overdose. 
In the event of an overdose, the investigator should: 
• Contact the Medical Monitor immediately. 
• Closely monitor the participant for AE/SAE and laboratory abnormalities until the 
study intervention can no longer be detected systemically (at least 5 half-lives but not 
less than 90 days). Document the quantity of the excess dose as well as the duration 
of the overdosing in the CRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
GSK does not recommend specific treatment for an overdose. 


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6.7. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
recreational drugs, vitamins, and/or herbal supplements) or other specific categories of 
interest that the participant is receiving at the time of enrolment 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 
The medical monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
Participants must abstain from taking prescription or non-prescription drugs (including 
vitamins, recreational drugs, and dietary or herbal supplements) within 7 days (or 14 days 
if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the 
start of study intervention until completion of the follow-up visit, unless, in the opinion of 
the investigator and sponsor, the medication will not interfere with the study.  
Paracetamol/Acetaminophen, at doses of  3 grams/day, is permitted for use any time 
during the study. Other concomitant medications may be considered on a case-by-case 
basis by the investigator in consultation with the medical monitor if required. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
This is a single dose study. In rare instances a participant may not be able to receive the 4 
injections and it may be necessary for the participant to permanently discontinue study 
intervention. If study intervention is discontinued, the participant will remain in the study 
for the planned duration.   
 
7.2. 
Study Stopping Criteria 
If any of the following occur, the study will be temporarily halted: 
 
• Any participant experiences a SAE that can be reasonably attributed to 
      GSK3858279. 
• Two or more participants experience the same significant clinical or significant 
laboratory abnormality that may plausibly relate to GSK3858279 (according to the 
clinical judgement of the investigator) 
• Two participants present with unexplained and clinically significant muco-cutaneous 
bleeding (according to the clinical judgement of the investigator and medical 
monitor) that is considered causally related to GSK 3858279 


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Recruitment may be resumed after appropriate review of safety findings by the Principal 
Investigators, Medical Monitor and SRT, and following approval to restart the study from 
the regulatory agencies and ethics committees 
 
7.2.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping, and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology See Section 10.6. 
Discontinuation of study intervention for abnormal liver tests is required when: 
• a participant meets one of the conditions outlined in the algorithm or  
•  in the presence of abnormal liver chemistry not meeting protocol-specified 
stopping rules, if the investigator believes that it is in the best interest of the 
participant.  
Phase 1 Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm 
 
 


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7.2.2. 
QTc Stopping Criteria 
A subject that meets either bulleted criterion based on the average of triplicate ECG 
readings will be withdrawn from study intervention.   
• 
QTcF > 500 msec, 
• 
Increase from baseline:  QTcF > 60 msec 
• 
In this study as QTcF is used for study eligibility, thus QTcF must be used for 
discontinuation decisions. 
• 
QTcF has been chosen for a participant’s eligibility, the same formula must 
continue to be used for that participant for all QTc data being collected for data 
analysis.  Safety ECGs and other non-protocol specified ECGs are an exception.   
• 
If an ECG demonstrates a prolonged QTc, obtain 2 more ECGs over a brief 
period (see Section), and then use the averaged QTc values of the 3 ECGs to 
determine whether the subject should be discontinued from the study 
• 
If a clinically significant finding is identified (including, but not limited to 
changes from baseline in QT interval corrected using Bazett’s formula [QTcB] 
or Fridericia’s formula [QTcF]]) after enrolment, the investigator or qualified 
designee will determine if the participant can continue in the study and if any 
change in participant management is needed. This review of the ECG printed at 
the time of collection must be documented. Any new clinically relevant finding 
should be reported as an AE. 
7.2.3. 
SARS-CoV-2 related stopping criteria 
N/A 
7.3. 
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, behavioural, 
or compliance reasons.  
• 
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. 
• 
The participant will be permanently discontinued from the study at that time. 
• 
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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7.4. 
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, 3 
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.  
 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA, see Section 1.3 
• Protocol waivers or exemptions are not allowed  
• Immediate safety concerns should be discussed with the sponsor immediately 
upon occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
• 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. 
• Safety/laboratory/analyte results that could unblind the study will not be reported 
to investigative sites or other blinded personnel until the study has been 
unblinded. 
• Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 


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8.1. 
Efficacy and/or Immunogenicity Assessments 
Efficacy assessments are not applicable to this study. 
Planned timepoints for all immunogenicity assessments are provided in the SoA. 
8.2. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA. 
8.2.1. 
Physical Examinations 
• A complete physical examination will include, at a minimum, assessments of the skin, 
cardiovascular, respiratory, gastrointestinal and neurological systems. Height (at 
screening only) and weight will also be measured and recorded. 
• A brief physical examination will include, at a minimum, assessments of the skin, 
lungs, cardiovascular system, and abdomen (liver and spleen). 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.2.2. 
Vital Signs 
• Temperature, pulse rate, respiratory rate, and blood pressure will be assessed 
following the site local procedures. 
• Blood pressure and pulse measurements will be assessed in semi supine position with 
a completely automated device. Manual techniques will be used only if an automated 
device is not available. 
• Blood pressure and pulse measurements should be preceded by at least 5 minutes of 
rest for the participant in a quiet setting without distractions (e.g., television, cell 
phones). 
• Vital signs (to be taken before blood collection for laboratory tests) will consist of 1 
pulse and 3 blood pressure measurements (3 consecutive blood pressure readings will 
be recorded at intervals of at least 1 minute). The average of the 3 blood pressure 
readings will be used to determine eligibility and be recorded on the CRF 
8.2.3. 
Electrocardiograms 
• Triplicate 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3) using 
an ECG machine that automatically calculates the heart rate and measures PR, QRS, 
QT, and QTc intervals. Refer to Section 7.2.2 for QTc withdrawal criteria and 
additional QTc readings that may be necessary. 
• At each timepoint at which triplicate ECGs are required, 3 individual ECG tracings 
should be obtained as closely as possible in succession, but no more than 2 minutes 
apart. 
 


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8.2.4. 
Clinical Safety Laboratory Tests 
• See Appendix 2 for the list of clinical laboratory tests to be performed and the SoA for 
the timing and frequency.  
• The investigator must review the laboratory report, document this review, and record 
any clinically significant changes occurring during the study as an AE. The laboratory 
reports must be filed with the source documents.  
• All laboratory tests with values considered clinically significantly abnormal during 
participation in the study after the last dose of study intervention should be repeated 
until the values return to normal or baseline or are no longer considered significantly 
abnormal by the investigator or medical monitor.  
• All protocol-required laboratory tests, as defined in Section 10.2, must be conducted in 
accordance with the laboratory manual and the SoA (Section 1.3 ). If laboratory values 
from non-protocol specified laboratory tests performed at the institution’s local 
laboratory require a change in participant management or are considered clinically 
significant by the investigator (e.g., SAE or AE or dose modification), then the results 
must be recorded. 
 
8.2.5. 
Echocardiogram  
A transthoracic echocardiogram will be performed at screening and repeated if clinically 
significant changes are observed at any time during the study treatment. Images will be 
obtained in standard views, the time to acquire images should not exceed approximately 
45 minutes.  
 
8.2.6. 
Skin Reactions 
Skin reactions will be recorded as AEs. The investigator will assess any skin reactions for 
their clinical significance and clinically significant skin reactions (as per investigator’s 
judgement) will be reviewed by a dermatologist and if appropriate a skin biopsy will be 
requested for histological analysis. Further technical details will be provided in the SRM. 
 


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8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Other Safety Reporting 
The definitions of adverse events (AEs) or serious adverse events (SAEs) can be found in 
Section 10.3 and Section 10.6. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, 
and recording events that meet the definition of an AE or SAE and remain responsible for 
following up all 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).  
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 / 
Section 10.6. 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• All SAEs will be collected from the start of intervention until the follow-up visit at 
the timepoints specified in the SoA (Section 1.3).  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 GSK product will be 
recorded from the time a participant consents to participate in the study.  
• All AEs will be collected from the start of intervention until the follow-up visit at the 
timepoints specified in the SoA (Section 1.3). 
• Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded as medical history/current medical 
conditions not as AEs. 
• 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 Appendix 3 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 information on AEs or SAEs after 
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. 
8.3.2. 
Method of Detecting AEs and SAEs 
• 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-
ended and nonleading verbal questioning of the participant is the preferred 
method to inquire about AE occurrence.  


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8.3.3. 
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 (as defined in Section 10.3), will be 
followed until the event is resolved, stabilized, otherwise explained, or the participant is 
lost to follow-up (as defined in Section 7.4). Further information on follow-up procedures 
is given in Section 10.3 / Section 10.6. 
8.3.4. 
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, Institutional Review Boards 
(IRBs)/Independent Ethics Committees (IECs), and investigators. 
• An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) 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 
 
8.3.5. 
Pregnancy 
• Details of all pregnancies in female partners of male participants will be collected 
after the start of study intervention and until time period for reporting pregnancies 
should align with the time period for post-intervention contraception determined in 
Section 10.4. 
• If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hoursof learning of the 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 and will be reported 
as such. 


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8.4. 
Pharmacokinetics 
Blood samples of approximately 3.5 mL will be collected for measurement of serum 
concentrations of GSK3858279 at the timepoints specified in the SoA. Each PK sample 
should be collected as close as possible to the planned time relative to the dose (i.e., time 
zero) administered to the participant on Day 1. The actual date and time of each dose and 
blood sample collection will be recorded. The timing of PK samples may be altered 
and/or PK samples may be obtained at additional time points to ensure thorough PK 
monitoring, if warranted and agreed upon between the investigator and the sponsor. 
Details on PK blood sample collection including processing, storage and shipping 
procures will be provided in the SRM. 
Serum analysis will be performed under the control of GSK Invitro/In vivo Translation 
(IVIVT). Serum concentrations of GSK3858279 will be determined using approved 
bioanalytical methodology. The bioanalytical site will be detailed in the relevant sample 
processing documents (e.g. SRM) and raw data will be archived in the GSK R&D GLP 
archives. Intervention concentration information that may unblind the study will not be 
reported to investigative sites or blinded personnel until the study has been unblinded. 
The timing of sample collections may be adjusted based on emerging data or other new 
information for this study to ensure optimal evaluation of PK. 
 
8.5. 
Target Engagement  
Blood samples (approximately 3.5mL) will be collected from participants in this study to 
investigate target engagement at the times specified in the SoA. Each TE sample should 
be collected as close as possible to the planned time relative to the dose (i.e., time zero) 
administered to the participant on Day 1. The actual date and time of each blood sample 
collection will be recorded. The timing of TE samples may be altered and/or TE samples 
may be obtained at additional time points to ensure thorough TE monitoring, if warranted 
and agreed upon between the investigator and the sponsor. The timing of sample 
collections may be adjusted based on emerging data or other new information for this 
study to ensure optimal evaluation of target engagement. Details of the processing, 
storage and shipping procedures for all samples are provided in the SRM. 
Serum samples will be collected for the evaluation of the free and total CCL17. CCL17 
can be detected in circulation and is the biological target for GSK3858279. The intention 
is to examine the relationship between free and total CCL17 and the effect of 
administration of GSK3858279 on the free and total levels of CCL17 in the circulation.  
Details of the sample collection including processing, storage and shipping procures will 
be presented in the SRM 
All samples will be retained for a maximum of 15 years after the last participant 
completes the study 


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8.6. 
Genetics 
Information regarding genetic research is included in Appendix 5. Genetic sampling is 
optional. Participants can refuse genetic sampling but will still be allowed to participate 
in the study. 
  
8.8. 
Immunogenicity Assessments 
Serum samples (approximately 5 mL) will be collected from all treated participants at 
pre-dose and various time points post-dosing, see SoA. Testing will be performed using 
the typical tiered approach involving screening, confirmation and titration assays [EMEA 
2017, FDA 2014], performed by Clinical Immunology, GlaxoSmithKline. If sera contain 
potential anti-GSK3858279 antibodies, they will be confirmed by immune-competition 
using excess drug, followed by a titration assay. Results will include the incidence of 
immunogenicity, antibody specificity and titres. 
For each participant, immunogenicity results, including the incidence and titres, will be 
reported. 
CCI


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9. 
STATISTICAL CONSIDERATIONS 
Complete details of the planned statistical analyses, including PK and TE parameter 
estimation, will be provided in the Statistical Analysis Plan (SAP). Any deviations from 
the planned analyses will be described in a SAP addendum or justified in the final clinical 
study report. 
9.1. 
Statistical Hypotheses 
The co- primary objectives of this study are: 
• 
To evaluate the safety and tolerability of a single SC dose of GSK3858279 compared 
with placebo administered to healthy participants  
• 
To assess the pharmacokinetic (PK) profile of a single SC dose of GSK3858279 in 
healthy participants  
No formal statistical hypotheses will be tested. 
 
 


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9.2. 
Analysis Sets 
Analysis Set 
Definition / Criteria 
Analyses 
Evaluated 
Screened 
All participants who were screened for eligibility. 
Study 
Population 
Enrolled 
All participants who entered the study, signed the 
ICF and were eligible for randomisation (regardless 
of whether the participant went on to be 
randomised).  
Note 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. 
Study 
Population 
Randomised  
All participants who were randomly assigned to 
study intervention in the study. 
Data will be reported according to the randomised 
study intervention. 
Study 
Population 
Safety 
All participants who received at least one injection 
of study intervention. 
Data will be reported according to the actual study 
intervention received. 
Safety 
Pharmacokinetic 
(PK)  
All participants in the safety population who 
received an active dose of study treatment and had 
at least one reportable PK assessment (Non-
quantifiable [NQ] values will be considered as 
reportable values). 
Participants will be analysed according to the study 
intervention they actually received. 
PK 
Target 
Engagement 
(TE) 
All participants in the safety population who had at 
least one reportable TE assessment (Non-
quantifiable [NQ] values will be considered as 
reportable values). 
Participants will be analysed according to the study 
intervention they actually received. 
TE 


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9.2.1. 
Statistical Analyses 
N/A 
9.2.2. 
General Considerations 
N/A 
9.2.3. 
Primary Endpoint(s) 
The following primary safety endpoints will be summarised descriptively by treatment 
group and cohort: the incidence of adverse events (AEs), serious adverse events (SAEs), 
withdrawals due to AEs, change from baseline in clinical laboratory parameters, vital 
signs, and cardiac parameters. 
Categorical data will be summarised with the number and percentage of participants in 
each category. Continuous data will be summarised with n, mean, standard deviation 
(SD), median, minimum and maximum. 
Primary analysis will be performed on the PK parameters AUC (0-56) post-dose and 
Cmax. The parameters will be loge transformed and then analysed using a mixed model, 
with ethnicity and body weight included as covariates. Geometric mean and 90% 
confidence intervals will be calculated for each of the ethnic cohorts, along with the 
comparisons for Japanese/Caucasians and Chinese/Caucasians. 
All other PK parameters will be summarised descriptively, with further details to be 
provided in the SAP. 
9.2.4. 
Secondary Endpoint 
TE parameters will be summarised descriptively, with further details to be provided in the 
SAP. 
9.2.5. 
Exploratory Endpoint(s) 
Further details of the exploratory analyses will be provided in the SAP. 
9.2.6. 
Interim Analyses  
Interim analyses may be performed, on data assessed in an unblinded manner, to support 
regulatory submissions. No changes to the conduct of the study will be implemented as a 
result of the analyses. If deemed necessary to conduct an interim, details will be 
documented in an interim charter prior to the unblinding, including what data will be 
reviewed, the level of unblinding (individual vs group summaries) and who will have 
access to the data. 


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9.3. 
Sample Size Determination 
Approximately 10 participants are to be randomized (7 active: 3 placebo) per cohort to 
ensure that a minimum of 6 participants on active and 2 on placebo per cohort are 
evaluable. An evaluable participant is one that has been dosed and has safety and all PK 
data up to Day 57. Replacements (assigned to the same treatment) are permitted at the 
discretion of the sponsor in consultation with the investigator.  
The sample size justification is based on simulations with the assumptions given below. 
Based on these assumptions, for a sample size of 6 evaluable participants receiving a 
 
 
 
 
 
 
CCI
CCI


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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: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) international ethical guidelines 
• Applicable ICH Good Clinical Practice (GCP) guidelines 
• 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: 
• 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 
• Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), ), European 
Medical Device Regulation 2017/745 for clinical device research (if 
applicable), and all other applicable local regulations 
 


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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 
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 or their legally authorized 
representative and answer all questions regarding the study.  
• Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative 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 centre.  
• 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 or their legally 
authorized representative  
• 
Participants who are rescreened are required to sign a new ICF. 
GSK (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 the study intervention or about the study disease; publish the results of these 
research efforts; work with government agencies or insurers to have the the study 
intervention approved for medical use or approved for payment coverage.  
 The ICF contains a separate section that addresses the use of participant data and 
remaining samples for optional further research. The investigator or authorised designee 
will inform each participant of the possibility of further research not related to the 
study/disease. Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period. A 
separate consent will be required to document a participant's agreement to allow any 
participant data and/or remaining leftover samples to be used for further research not 
related to the study/disease by ticking of a corresponding “Yes” box. Participants who 
decline further research will tick the corresponding “No” box. 


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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 which 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. 
10.1.5. 
Committees Structure 
N/A 
10.1.6. 
Early Safety Data Review AND/OR Committee 
• Case unblinding may be performed for above reviews if necessary. 
 
10.1.7. 
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 GSK site or other 
mutually-agreeable location. 
• 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(s) is/are encouraged to share the summary results with the 
study subjects, as appropriate. 
• Under the framework of the SHARE initiative, 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. 
• GSK will provide the investigator with the randomization codes for their site only 
after completion of the full statistical analysis. 


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• 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 GSK Policy. 
• GSK intends to make anonymized patient-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 
• A manuscript will be progressed for publication in the scientific literature if the results 
provide important scientific or medical knowledge. 
 
10.1.8. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic 
CRFs unless transmitted to the sponsor or designee electronically (e.g., laboratory 
data). The investigator is responsible for verifying that data entries are accurate and 
correct by physically or electronically signing the CRF.  
• Guidance on completion of CRFs will be provided in the SRM 
• Quality tolerance limits (QTLs) will be pre-defined in the QTL Plan 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 noncompliance 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. 
• The sponsor assumes accountability for actions delegated to other individuals (e.g., 
contract research organizations). 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF 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 


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• Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for 30 years from the issue of the final Clinical 
Study Report (CSR)/ 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.  
• A retention period of 30 years instead of 25 years is used, as the long-term effects of 
GSK3858279 are still unknown and the to be included healthy volunteers could be of 
relatively young age; thus, still with a long life-expectancy 
10.1.9. 
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 CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be 
explained. The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available. 
• 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 in the CRF. 
 
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 healthy participant to be screened is considered the first act of recruitment and 
will be the study start date. 
Study/Site Termination 
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 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. 


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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 
contract research organization(s) used in the study of the reason for termination or 
suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the subject 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 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 Clinical Safety Laboratory Tests 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC count with 
differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistry1 
Urea 
Potassium 
Aspartate 
aminotransferase 
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase 
(SGOT) 
Total and direct 
bilirubin 
 
Creatinine 
Sodium 
Alanine 
aminotransferase 
 (ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase 
(SGPT) 
Total protein 
 
Glucose non-
fasting 
Calcium 
Alkaline 
phosphatase2 
 
Routine 
Urinalysis 
• Specific gravity 
• pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, 
leukocyte esterase by dipstick 
• Microscopic examination (if blood or protein is abnormal) 


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Laboratory 
Assessments 
Parameters 
Other 
Screening 
Tests 
• Follicle-stimulating hormone (as needed in women of nonchildbearing 
potential only) 
• Breath Alcohol test 
• Urine drug screen (to include at minimum: amphetamines, barbiturates, 
cocaine, opiates, cannabinoids and benzodiazepines  
• HIV antibody, hepatitis B surface antigen [HBsAg], hepatitis B core 
antibody [HbcAb] and hepatitis C virus antibody. 
• QuantiFERON test 
• Urine albumin-creatinine ratio (UACR) 
• Complement C3 and C4 
• 
3SARS-CoV2 PCR or rapid antigen test 
The results of each test must be entered into the medical notes 
Other 
Screening and 
Follow-Up 
Tests 
• Troponin-I (high sensitivity) 
• NT-proBNP 
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 7.1 and Section 10.6 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 
GSK in an expedited manner (excluding studies of hepatic impairment or cirrhosis). 
2. 
If alkaline phosphatase is elevated, consider fractionating. 
3. 
Combined throat and nasopharyngeal swab or nasal swab only; qPCR or rapid antigen test as per unit 
coronavirus test vendor protocol  
. 
 


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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. 
 
Events Meeting the AE Definition 
For efficacy studies, include the penultimate bullet, and for non-efficacy studies involving 
marketed products in established indications, include the final bullet. 
• 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. 


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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. 
 
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. 


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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≥3xULN AND total bilirubin ≥2xULN (>35% 
direct bilirubin) or international normalized ratio (INR) >1.5 must be reported 
as 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. 
o Examples of such events include invasive or malignant cancers, 
intensive treatment for allergic bronchospasm, blood dyscrasias, 
convulsions, or development of intervention dependency or intervention 
abuse. 
 


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10.3.3. 
Recording and Follow-Up of AE and SAE 
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 GSK in lieu of completion of the GSK required form. 
• There may be instances when copies of medical records for certain cases are 
requested by 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 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 Investigator’s Brochure (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 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 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. 
 
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 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 GSK with a copy of any post-mortem 
findings including histopathology.  
• New or updated information will be recorded in the originally submitted 
documents. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 


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10.3.4. 
Reporting of SAE to GSK 
SAE Reporting to 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 by telephone. 
• 
Contacts for SAE reporting can be found in SRM 
 
SAE Reporting to 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  
• 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 in SRM 
 


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10.4. 
Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. 
Definitions of Women of child bearing potential and Women of 
non-child bearing potential: 
WOCBP (NB: WOCBP are not permitted to participate in the study) 
A woman 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. 
 
Women in the following categories are considered WONCBP 
1. Premenopausal female with permanent infertility due to one of the following (for the 
purpose of this study): 
a) Documented hysterectomy 
b) Documented bilateral salpingectomy 
c) Documented bilateral oophorectomy 
• 
For individuals with permanent infertility due to an alternate medical cause 
other than the above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal 
dysgenesis), 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. 
2. 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 may 
be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, confirmation with more than one FSH measurement is 
required. 
o In addition, females under the age of 55 years must have a documented serum 
follicle stimulating hormone (FSH) level > 40mIU/mL to confirm menopause. 
o Females on HRT and whose menopausal status is in doubt must discontinue HRT 
to allow confirmation of postmenopausal status before study enrolment. 
 
 
 
 
 


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10.4.2. 
Contraception Guidance 
Males must use the male condom and should be advised of the benefit for a partner to use 
a highly effective method of contraception as outlined below. 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency  
• 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)c 
• 
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 woman 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 Methodsb That Are User Dependent 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
• 
oral 
• 
intravaginal 
• 
transdermal 
• 
injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
• 
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 
a. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. 
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
c. 
Male condoms must be used in addition to hormonal contraception If locally required, in accordance with 
Clinical Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited to those 
which inhibit ovulation as the primary mode of action. 
 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), only, 
and lactational amenorrhoea method (LAM) are not acceptable methods of contraception for this study. Male 
condom and female condom should not be used together (due to risk of failure with friction) 
 
 
 


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10.4.3. 
Collection of Pregnancy Information: 
Male participants with partners who become pregnant 
• 
Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while 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 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 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 
 
 


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10.5. 
Appendix 5: Genetics 
• USE/ANALYSIS OF DNA Genetic variation may impact a participant’s response to 
study intervention, susceptibility, severity and progression of disease. Variable 
response to study intervention may be due to genetic determinants that impact drug 
absorption, distribution, metabolism, and excretion; mechanism of action of the drug; 
disease etiology; and/or molecular subtype of the disease being treated. Therefore, 
where local regulations and IRB/IEC allow, a blood sample will be collected for 
DNA analysis 
• DNA samples will be used for research related to study intervention They may also 
be used to develop tests/assays including diagnostic tests) related to study 
intervention]. Genetic research may consist of the analysis of one or more candidate 
genes or the analysis of genetic markers throughout the genome [or analysis of the 
entire genome (as appropriate) 
• Additional analyses of DNA samples may be conducted if it is hypothesized that this 
may help further understand the clinical data.  
• The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.  
• The samples will be retained while research on study intervention (or study 
interventions of this class) continues but no longer than 15 years after the last subject 
last visit or other period as per local requirements. 
 
 


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10.6. 
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments  
Phase 1 Liver chemistry stopping criteria have been designed to assure subject safety and 
to evaluate liver event aetiology.  
Phase 1 liver chemistry stopping criteria and required follow up assessments 
Liver Chemistry Stopping Criteria  
 
ALT-absolute 
 
ALT≥3xULN 
If ALT≥3xULN AND bilirubin1,2  2xULN (>35% direct bilirubin) or 
international normalized ratio (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 discontinue study intervention 
• Report the event to GSK within 24 hours 
• Complete the liver event CRF, 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, stabilise, or return to 
within baseline (see MONITORING below) 
MONITORING: 
If ALT≥3xULN AND bilirubin  2xULN or INR 
>1.5 
• Repeat liver chemistries (include ALT, 
aspartate transaminase [AST], alkaline 
phosphatase, bilirubin and INR) and 
perform liver event follow up assessments 
within 24 hours 
• Monitor participant twice weekly until liver 
chemistries resolve, stabilise or return to 
within baseline 
• A specialist or hepatology consultation is 
recommended 
• Viral hepatitis serology3 
• 
Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward 
trend 
• Obtain blood sample for pharmacokinetic 
(PK) analysis as soon as possible, and at 
least within 7 days, post last dose4  
• Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH). 
• Fractionate bilirubin, if total 
bilirubin2xULN 
• 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 case report form 


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Liver Chemistry Stopping Criteria  
 
If ALT≥3xULN AND bilirubin < 2xULN and 
INR ≤1.5: 
• Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin and INR) 
and perform liver event follow up 
assessments within 24-72 hours 
• Monitor participant weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
If ALT≥3xULN AND bilirubin  2xULN or 
INR >1.5: 
• Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total immunoglobulin G (IgG) or gamma 
globulins. 
Serum acetaminophen adduct high 
performance liquid chromatography 
(HPLC) assay (quantifies potential 
acetaminophen contribution to liver injury 
in subjects with definite or likely 
acetaminophen use in the preceding 
week) [James, 2009].  
• Liver imaging (ultrasound, magnetic 
resonance, or computerised tomography) 
and /or liver biopsy to evaluate liver 
disease; complete Liver Imaging and/or 
Liver Biopsy CRF forms. 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention for that subject if ALT  3xULN and bilirubin  2xULN. 
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  3xULN and bilirubin  2xULN (>35% direct bilirubin) or ALT  3xULN 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 subjects receiving anticoagulants 
3. Includes: Hepatitis A immunoglobulin (gM) antibody; HBsAg and HBcAb; 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. PK sample may not be required for participants known to be receiving placebo or non-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 on the CRF. 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 SRM 
 
 
 
 
 


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10.7. 
Appendix 7: Abbreviations and Definitions and Trademarks 
Abbreviations 
ADA 
Anti-Drug Antibody 
AE 
Adverse Event 
AUC 
Area Under the concentration-time Curve 
BMI 
Body Mass Index 
BUN 
Blood Urea Nitrogen 
CA 
Competent Authority 
CCL17 
Chemokine C-C motif ligand 17 
CFR 
Code of Federal Regulation 
CIOMS 
Council for International Organizations of Medical Sciences 
Cmax  
Maximum Observed Concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
Coronavirus Disease 2019 
CPK 
Creatine Phosphokinase 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EMA 
European Medicines Agency  
FDA 
Food and Drug Administration 
FiH 
First in Human 
GCP 
Good Clinical Practice 
GSK 
GlaxoSmithKline 
HBcAb 
Hepatitis B Core Antibody 
HBsAg 
Hepatitis B Surface Antigen 
HIV 
Human Immunodeficiency Virus 
HPLC 
High-Performance Liquid Chromatography 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IgA 
Immunoglobulin A 
IgM 
Immunoglobulin G 
INR 
International Normalized Ratio 
IP  
Investigational Product 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Recognition System 
kg 
Kilogram 
LDH 
Lactate Dehydrogenase 
mAb 
Monoclonal Antibody 
MCH 
Mean Corpuscular Haemoglobin 


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MRCT 
Multiregion Randomised Clinical Trial 
MCV 
Mean Corpuscular Volume 
mg 
Milligram 
mL 
Milliliter  
MSDS 
Material Safety Data Sheet 
NIMP 
Non-Investigational Medicinal Product 
NSAID 
Non-Steroidal Anti-Inflammatory Drug 
OA 
Osteoarthritis 
PBO 
Placebo 
PGx 
Genetics Sample 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
PPE 
Personal Protective Equipment  
QTc 
Electrocardiogram QT interval corrected for heart rate 
QTcB 
Electrocardiogram QT interval corrected for heart rate using Bazett’s formula 
QTcF 
Electrocardiogram QT interval corrected for heart rate using Fridericia’s 
formula 
RAMOS NG 
Randomization and Medication Ordering System Next Generation 
RAP 
Reporting and Analysis Plan 
RBC 
Red Blood Cells 
RNA 
Ribonucleic Acid 
SAE 
Serious Adverse Event 
SARS-Cov-2 
Severe acute respiratory syndrome– Coronavirus-2 
SC 
Subcutaneous 
sec 
Seconds 
SGOT 
Serum Glutamic-Pyruvic Transaminase 
SGPT 
Serum Glutamic-Pyruvic Transaminase 
SMG 
Safety and Medical Governance 
SRM 
Study Reference Manual 
SoA 
Schedule of Activities 
TARC 
Thymus and Activation Regulated Chemokine 
TB 
Tuberculosis 
TDAR 
T-cell Dependent Antibody Response 
TE 
Target Engagement 
tmax 
Time of Occurrence of Maximum Observed Drug Concentration 
UACR 
Urine albumin-creatinine ratio 
UK 
United Kingdom 
ULN 
Upper Limit of Normal  
WBC 
White Blood Cells 
WOCBP 
Woman of Childbearing Potential 
WONCBP 
Woman of Non-childbearing Potential 
 
 
 


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10.8. 
Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Amendment 1 11-JAN-2022 
Overall Rationale for the Amendment:  
This is a protocol amendment with changes to the inclusion/exclusion criteria, assessment 
time points, clarification regarding consent to further research, clarification regarding 
alcohol consumption and tobacco use, changes to the protocol title to align with eTrack 
and correction of typographical errors.  These amendments were made following 
feedback from the study site and HREC. 
 


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Section # 
and Name 
Description of Change 
Brief Rationale 
Global 
Change  
Troponin-T updated to Troponin I” 
throughout protocol  
Troponin T and Troponin I have similar 
diagnostic accuracy. 
1.1 Overall 
Design  
Updated text – ‘To try to eliminate 
any time dependant variability 
among ethnic groups, we will aim 
to treat Caucasian and Asian 
groups concurrently.    
This amendment was made for 
clarification 
1.3 Schedule 
of Activities 
Estradiol removed from screening 
period table  
FSH is sufficient to confirm menopause as 
specified in Section 10.4  
1.3 Schedule 
of Activities 
 
 
Aid with participant compliance to the 
study schedule.  
1.3 Schedule 
of Activities 
Outpatient visit removed from Day 
-1. 
 
Error in original protocol.  Participants will 
be admitted on Day -1 for an overnight 
stay. 
1.3 Schedule 
of Activities 
Footnotes 4 and 5 removed from 
Day -1 12 Lead ECG and Vital 
signs tests 
These were present in error in the original 
protocol.   
1.3 Schedule 
of Activities 
COVID PCR, footnote 7 removed 
from Day 57, 
 and Early 
Withdrawal visits. 
Error in original protocol, footnote applies 
to Day -2 visit only 
1.3 Schedule 
of Activities 
- PD 
Footnote 10 removed from Day 1 
for Serum/Plasma for protein and 
PD for transcriptomic analysis. 
Error in original protocol, footnote 10 
applies to PK and TE samples only. 
5.1 Inclusion 
Criteria  
Inclusion Criteria #5  
Updated to widen the BMI range 
for Caucasian participants 
This amendment was made to maximise 
the Caucasian participant pool.    
5.2 
Exclusion 
Criteria  
Exclusion Criterion #12. 
Typographical error Bazett’s” 
formula is shown as QTcF in 
protocol, this has been corrected 
to QTcB 
This amendment was made to correct 
typographical errors. 
5.2 
Exclusion 
Criteria  
Exclusion Criterion #18 - Added 
details about enzyme inducers 
and allowed medications directly 
into the exclusion criteria  
This will ensure that participants are not 
included in the study when they are not 
allowed or excluded when they could 
potentially be eligible. 
CCI
CCI


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Section # 
and Name 
Description of Change 
Brief Rationale 
5.2 
Exclusion 
Criteria 
Exclusion Criterion #35 – 
Amended the definition of an 
average weekly intake of 
alcohol to:  >11 standard 
drinks for males and females. 
One standard drink contains 
10g of alcohol 
This amendment was made as requested 
by HREC 
5.3.3 
Caffeine 
Alcohol and 
Tobacco 
Text updated ‘participants 
should not consume more 1.5 
standard drinks of alcohol 
daily on average (10g alcohol 
in 1 Australian standard drink)’ 
This amendment was made as requested 
by HREC 
5.3.3 
Caffeine 
Alcohol and 
Tobacco 
Protocol text update adding ‘Non-
smokers or light smokers <= 5 
cigarettes / nicotine-forms per 
week) may be enrolled in the trial. 
Light smokers must abstain from 
nicotine containing products for at 
least 3 days prior to Day 1 dosing 
and for the duration of the 
inpatient stay’ 
 
Updated text to allow light smokers to 
participate in the study 
8.2.2. Vital 
Signs  
Text added to state the average of 
triplicate blood pressure 
measurements confirms 
participant eligibility. 
This amendment was made for 
clarification 
10.1.3 
Informed 
Consent 
Process 
Updated the protocol text 
replacing the requirement for a 
separate signature in the ICF to 
allow use of participant data 
and/or remaining leftover samples 
to be used for further research not 
related to the study/disease with a 
tick corresponding ‘Yes’ box  
This amendment clarified the 
inconsistency in wording regarding 
consent between the ICF and the protocol 
for further use of participant data and or 
remaining leftover sample. 
Appendix 2: 
Clinical 
Laboratory 
Tests 
Table 2: Test for estradiol levels 
removed.  
FSH is sufficient to confirm menopause as 
specified in Section 10.4  
 


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Section # 
and Name 
Description of Change 
Brief Rationale 
Trademark 
Information 
Additional table added for 
Trademarks not owned by the 
GlaxoSmithKline group of 
companies 
Amendment made as requirement of 
protocol template  
 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
RAMOS NG 
 
None 
 
 
 


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11. 
REFERENCES 
Bouma G, Zamuner S, Hicks K, et al. CCL20 neutralization by a monoclonal antibody in 
healthy subjects selectively inhibits recruitment of CCR6+ cells in an experimental 
suction blister. Br J Clin Pharmacol. 2017; 83(9); 1976-1990. 
EMEA/CHMP/BMWP/14327/2006 Rev 1 Committee for Medicinal Products for Human 
Use (CHMP) Guideline on Immunogenicity assessment of therapeutic proteins, 18 May 
2017. 
FDA Guidance for Industry, Immunogenicity Assessment for Therapeutic Protein 
Products U.S. Department of Health and Human Services, Food and Drug 
Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics 
Evaluation and Research (CBER), August 2014. 
Gear AR, Suttitanamongkol S, Viisoreanu D, et al. Adenosine diphosphate strongly 
potentiates the ability of the chemokines MDC, TARC, and SDF-1 to stimulate platelet 
function. Blood. 2001; 97(4); 937-45. 
GSK Document Number TMF-14447953 A two-part phase I randomized, double-blind, 
placebo-controlled study to evaluate safety, tolerability, pharmacokinetics and target 
engagement of single intravenous and subcutaneous doses of GSK3858279 in healthy 
participants and to evaluate the efficacy of repeat subcutaneous doses in participants with 
osteoarthritis of the knee. Effective 09 FEB 2022. 
GSK Document Number 2020N429762_00 Interim Report of blinded data from Part A of 
Study 207804: A two-part phase I randomized, double blind, placebo-controlled study to 
evaluate safety, tolerability, pharmacokinetics and target engagement of single 
intravenous and subcutaneous doses of GSK3858279 in healthy participants. Effective 07 
SEP 2020. 
GSK3858279 Investigator's Brochure RPS-CLIN-014604 V05 Effective 02 JUL 2021. 
Hagemann UB, Gunnarsson L, Geraudie S, et al. Fully human antagonistic antibodies 
against CCR4 potently inhibit cell signaling and chemotaxis. PLoS One. 2014; 9(7); 
e103776.  
Imai T, Baba M, Nishimura M, et al. The T cell-directed CC chemokine TARC is a 
highly specific biological ligand for CC chemokine receptor 4. J Biol Chem. 1997; 
272(23); 15036-15042. 
Imai T, Yoshida T, Baba M, et al. Molecular cloning of a novel T cell-directed CC 
chemokine expressed in thymus by signal sequence trap using Epstein-Barr virus vector. 
J Biol Chem. 1996; 271(35); 21514-21521. 
James LP, Letzig L, Simpson PM, et al. Pharmacokinetics of Acetaminophen-Adduct in 
Adults with Acetaminophen Overdose and Acute Liver Failure. Drug Metab Dispos 
2009; 37:1779-1784 


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Kara E, Comerfield I, Fenix K, et al. Tailored Immune Responses: Novel Effector Helper 
T Cell Subsets in Protective Immunity. PloS Pathogens. 2014; 10: 1-15 
Kronenberg S, Husar E, Schubert C, et al. Comparative assessment of immune complex-
mediated hypersensitivity reactions with biotherapeutics in the non-human primate: 
Critical parameters, safety and lessons for future studies. Regul Toxicol Pharmacol. 2017; 
88: 125-137. 
Specht S, Frank JK, Alferink J, et al. CCL17 controls mast cells for the defense against 
filarial larval entry. J Immunol. 2011; 186(8); 4845-52. 

SAP_001.pdf: 
Statistical Analysis Plan
Study ID:  212979
Official Title of Study: A Randomised, Double-blind, Placebo-controlled Study of 
the Safety,Tolerability, Pharmacokinetics, Target Engagement and Immunogenicity 
of a single subcutaneous dose of GSK3858279 administered to Healthy Caucasian, 
Chinese and Japanese Participants.
Date of Document: 28-NOV-2022


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
212979 
 
 
Page 1 of 29 
 
XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021 
Information Type: 
Statistical Analysis Plan (SAP) 
 
TITLE PAGE 
Protocol Title: 
A Randomised, Double-blind, Placebo-controlled Study of the 
Safety, Tolerability, Pharmacokinetics, Target Engagement and 
Immunogenicity of a single subcutaneous dose of GSK3858279 
administered to Healthy Caucasian, Chinese and Japanese 
Participants.  
Study Number: 
212979  
Compound Number: 
GSK3858279  
Abbreviated Title: 
Safety, tolerability, pharmacokinetics and target engagement of 
GSK3858279 after a single subcutaneous dose in healthy 
Caucasian, Chinese and Japanese participants 
 
Sponsor Name: GlaxoSmithKline Research & Development Limited  
Regulatory Agency Identifier Number(s) TBC 
 
 
Copyright 2022 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 


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XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021 
TABLE OF CONTENTS 
PAGE 
TABLE OF CONTENTS .................................................................................................. 2 
1. 
INTRODUCTION ...................................................................................................... 5 
1.1. 
Objectives, Estimands and Endpoints ........................................................... 5 
1.2. 
Study Design ................................................................................................ 7 
2. 
STATISTICAL HYPOTHESES ................................................................................. 8 
2.1. 
Multiplicity Adjustment .................................................................................. 8 
3. 
ANALYSIS SETS ..................................................................................................... 9 
4. 
STATISTICAL ANALYSES ..................................................................................... 10 
4.1. 
General Considerations .............................................................................. 10 
4.1.1. 
General Methodology .................................................................. 10 
4.1.2. 
Baseline Definition ....................................................................... 10 
4.2. 
Primary Endpoints Analyses ....................................................................... 10 
4.2.1. 
Pharmacokinetics ........................................................................ 11 
4.2.2. 
Safety .......................................................................................... 12 
4.2.3. 
Sensitivity analyses ..................................................................... 13 
4.3. 
Secondary Endpoint(s) Analyses ................................................................ 13 
4.3.1. 
Target Engagement ..................................................................... 13 
4.3.2. 
Anti-drug antibody (ADA) formation ............................................. 14 
4.3.3. 
Sensitivity analyses ..................................................................... 14 
4.4. 
Exploratory Endpoint Analyses ................................................................... 14 
4.5. 
Safety Analyses .......................................................................................... 16 
4.5.1. 
Adverse Events............................................................................ 16 
4.5.2. 
Additional Safety Assessments .................................................... 17 
4.6. 
Other Analyses ........................................................................................... 18 
4.6.1. 
Subgroup analyses ...................................................................... 18 
4.7. 
Interim Analyses ......................................................................................... 18 
4.7.1. 
Day 57 Analysis ........................................................................... 19 
4.7.2. 
Other ........................................................................................... 19 
4.8. 
Changes to Protocol Defined Analyses ....................................................... 19 
5. 
SAMPLE SIZE DETERMINATION ......................................................................... 20 
6. 
SUPPORTING DOCUMENTATION ....................................................................... 22 
6.1. 
Appendix 1 Study Population Analyses ....................................................... 22 
6.1.1. 
Participant Disposition ................................................................. 22 
6.1.2. 
Demographic and Baseline Characteristics .................................. 22 
6.1.3. 
Protocol Deviations ...................................................................... 22 
6.1.4. 
Prior and Concomitant Medications ............................................. 23 
6.1.5. 
Additional Analyses Due to the COVID-19 Pandemic .................. 23 
CCI


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XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021 
6.2. 
Appendix 2 Data Derivations Rule .............................................................. 24 
6.2.1. 
Criteria for Potential Clinical Importance ...................................... 24 
6.2.2. 
Study Phase ................................................................................ 25 
6.2.3. 
Study Day and Reference Dates .................................................. 25 
6.2.4. 
Assessment Window ................................................................... 26 
6.2.5. 
Multiple measurements at One Analysis Time Point .................... 26 
6.2.6. 
Handling of Partial Dates ............................................................. 26 
7. 
REFERENCES ....................................................................................................... 29 
 


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XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021 
Version history 
  
SAP Version 
Approval Date 
Protocol 
Version (Date) 
on which SAP 
is Based 
Change 
Rationale 
SAP 
10 May 2022 
Protocol 
Amendment 02 
(29-APR-2022) 
Not Applicable 
Original 
version 
SAP 
Amendment 1 
28 Nov 2022 
Protocol 
Amendment 02 
(29-APR-2022) 
Update to 
Objectives and 
Endpoints table 
Changes to 
objectives not 
made in 
original 
version 
following 
protocol 
amendment 2 
 
 
 
Removal of 
sentence 
specifying 
Anatomical 
Therapeutic 
Chemical 
(ATC) 
classifications 
will not appear 
in summaries 
Decision to 
include ATC 
classification
s in 
summaries 
 
 
 
Inclusion of 
details of 
additional 
interim analysis 
Decision 
made to 
conduct 
additional 
interim 
analysis for 
this study to 
support 
regulatory 
submissions 
 


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1. 
INTRODUCTION 
The purpose of this SAP is to describe the planned analyses to be included in the CSR for 
Study 212979.  
1.1. 
Objectives, Estimands and Endpoints 
Objectives 
Endpoints 
Primary 
 
• 
To evaluate the safety and tolerability 
of a single SC dose of GSK3858279 
compared with placebo administered 
to healthy participants including 
cohorts of Japanese, Chinese and 
Caucasians 
• 
Incidence of adverse events (AEs), 
serious adverse events (SAEs), 
withdrawals due to AEs 
• 
Occurrence of clinically important 
changes from baseline in clinical 
laboratory parameters (haematology, 
clinical chemistry, urinalysis), vital 
signs (blood pressure, heart rate, body 
temperature), and cardiac parameters 
(electrocardiogram)  
• 
To assess the pharmacokinetic (serum 
PK) profile up to 56 days following a 
single SC dose of GSK3858279 in 
healthy participants including cohorts 
of Japanese, Chinese and Caucasians 
• 
PK parameters: area under the 
concentration-time curve (AUC(0-56), 
AUC(0-t) post-dose), time of 
occurrence of last quantifiable 
concentration (tlast), maximum 
observed concentration (Cmax), and 
time of occurrence of Cmax (tmax) per 
cohort as data permits 
Secondary 
 
• 
To evaluate target engagement (TE) up 
to 56 days following a single SC dose 
of GSK3858279 in healthy participants 
including cohorts of Japanese, Chinese 
and Caucasians.  
• 
Reduction (%) from baseline in free 
CCL17: maximum, minimum and at 
Days 7, 14, 28 and 56 post-dose 
• 
Total CCL17 (free and when bound to 
GSK3858279): maximum observed 
concentration (Cmax), time of Cmax 
(tmax), maximum fold increase 
compared to baseline, fold increase 
compared to baseline at Days 7, 14, 28 
and 56 post-dose. 
• 
To assess the potential for anti-drug 
• 
Incidence of pre-existing ADAs 


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Objectives 
Endpoints 
antibody (ADA) formation 
• 
Incidence of treatment-emergent 
ADAs over time (and whether 
neutralising) 
Exploratory 
 
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1.2. 
Study Design 
Overview of Study Design and Key Features 
Design 
Features 
• 
This is a Ph1 Randomised, Double-blind, Placebo-controlled Study of 
the Safety, Tolerability, Pharmacokinetics, Target Engagement and 
Immunogenicity of a single subcutaneous dose of GSK3858279 
administered to Healthy Caucasian, Chinese and Japanese Participants. 
• 
The total duration of this study is not expected to exceed a maximum 
of 
: (Screening [up to 28 days] and a follow-up period of 
. Follow-up may be extended if a serious or clinically 
significant AE 
. 
• 
The primary PK and TE analysis for this study will occur once all 
participants have completed Day 57. An interim analysis of safety will 
also be conducted at this time. 
Study 
intervention 
Study intervention will be administered on Day 1 as four separate SC 
injections of either GSK3858279 (
 or Placebo.  
Study 
intervention 
Assignment 
Cohorts of Caucasian, Chinese and Japanese participants will be 
randomised to GSK3858279 
 or Placebo in a 7:3 ratio, 
respectively for each cohort. 
Interim 
Analysis 
Interim analysis of Safety data will occur alongside primary PK and TE 
analysis at Day 57. Additional interim analyses may be performed on data 
assessed in an unblinded manner, to support regulatory submissions. No 
changes to the conduct of the study will be implemented as a result of the 
analyses. 
 
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2. 
STATISTICAL HYPOTHESES  
The co- primary objectives of this study are: 
• 
To evaluate the safety and tolerability of a single SC dose of GSK3858279 compared 
with placebo administered to healthy participants including cohorts of Japanese, 
Chinese and Caucasians  
• 
To assess the pharmacokinetic (PK) profile of a single SC dose of GSK3858279 in 
healthy participants including cohorts of Japanese, Chinese and Caucasians 
No formal statistical hypotheses will be tested. 
2.1. 
Multiplicity Adjustment 
There will be no adjustments for multiplicity. 
 


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3. 
ANALYSIS SETS 
Analysis Set 
Definition / Criteria 
Analyses 
Evaluated 
Screened 
All participants who were screened for eligibility. 
Study 
Population 
Enrolled 
All participants who entered the study, signed the 
ICF and were eligible for randomisation (regardless 
of whether the participant went on to be randomised).  
Note 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. 
Study 
Population 
Randomised  
All participants who were randomly assigned to 
study intervention in the study. 
Data will be reported according to the randomised 
study intervention. 
Study 
Population 
Safety 
All participants who received at least one injection of 
study intervention. 
Data will be reported according to the actual study 
intervention received. 
Safety 
Pharmacokinetic 
(PK)  
All participants in the safety population who received 
an active dose of study treatment and had at least one 
reportable PK assessment (Non-quantifiable [NQ] 
values will be considered as reportable values). 
Participants will be analysed according to the study 
intervention they actually received. 
PK 
Target 
Engagement 
(TE) 
All participants in the safety population who had at 
least one reportable TE assessment (Non-quantifiable 
[NQ] values will be considered as reportable values). 
Participants will be analysed according to the study 
intervention they actually received. 
TE 
 


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4. 
STATISTICAL ANALYSES 
4.1. 
General Considerations 
4.1.1. 
General Methodology 
Participants who withdraw from the study may be replaced, with any replacements 
beginning from the start of the study. 
Summary tables will provide the following descriptive statistics as a minimum, unless 
otherwise specified: 
• Continuous data (normally distributed):  
n, mean, standard deviation (SD), median, minimum and maximum. 
 
• Continuous data (log-normally distributed):  
n, geometric mean, SD on the log scale (SD (log)), median, minimum and 
maximum. 
 
• Categorical data: 
number and percentage of participants in each category. 
 
4.1.2. 
Baseline Definition 
For all endpoints the baseline value will be the latest pre-dose assessment with a non-
missing value, including those from unscheduled visits. If time is not collected, Day 1 
assessments are assumed to be taken prior to first dose and used as baseline. 
The CCL17 levels (free, total) baseline value will be derived by averaging the two pre-
dose measurements (Day -2 and Day 1 pre-dose). 
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
 
4.2. 
Primary Endpoints Analyses 
The primary endpoints for this study are: 
• 
Incidence of AEs, SAEs, withdrawals due to AEs 
• 
Occurrence of clinically important changes from baseline in clinical laboratory 
parameters (haematology, clinical chemistry, urinalysis), vital signs (blood pressure, 
heart rate, body temperature), and cardiac parameters (electrocardiogram) 
• 
PK parameters: area under the concentration-time curve (AUC(0-56), AUC(0-t)), 
time of occurrence of last quantifiable concentration (tlast), maximum observed 


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concentration (Cmax), and time of occurrence of Cmax (tmax) per cohort as data 
permits 
 
4.2.1. 
Pharmacokinetics  
All PK analyses will be performed on the PK population. Serum GSK3858279 
concentration-time data will be analysed by non-compartmental and/or model-based 
methods, as appropriate. Calculations will be based on the actual sampling times recorded 
during the study. Concentration-time data will be listed for each participant and 
summarized by planned time point and cohort. The following summary statistics will be 
calculated for each cohort: 
• 
Geometric mean, 95% CI of the geometric mean, SD(log), median , min and max 
Individual serum concentration-time data and summary data will be graphically 
displayed.  
From the serum concentration-time data collected up to Day 57, the following PK 
parameters will be determined, as data permit:  
• 
Area under the serum concentration-time curve (AUC(0-56), AUC(0-t)) 
• 
Time of last quantifiable concentration (tlast) 
• 
Maximum observed concentration (Cmax)  
• 
Time of occurrence of Cmax (tmax)  
 
4.2.1.1. 
Summary Measures of Derived Parameters 
PK parameters will be listed for each participant and summarized descriptively by cohort. 
For each of these parameters, except for tmax and tlast, the following summary statistics 
will be calculated for each cohort:  
• 
Median, maximum, minimum, arithmetic mean and standard deviation of non-
transformed data.  
• 
Geometric mean, 95% confidence interval (CI) for the geometric mean, standard 
deviation and coefficient of variation of logarithmically transformed data.  
For tmax and tlast, arithmetic mean, standard deviation, median, maximum and minimum 
will be calculated.  
 


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4.2.1.2. 
Statistical Analysis 
Table 1 
Statistical Analysis of Primary Endpoint(s) 
Endpoint  
• 
AUC(0-56) 
• 
Cmax 
Model Specification 
• 
The PK parameters will be loge transformed and analysed using a mixed model.  
• 
Terms fitted in the model will include ethnicity and loge(body weight). 
• 
An additional model including the ethnicity term only will be fitted. 
Model Checking & Diagnostics 
• 
Normality assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals and a plot of the residuals versus 
the fitted values (i.e. checking the normality assumption and constant variance 
assumption of the model, respectively) to gain confidence that the model 
assumptions are reasonable. 
• 
If there are any departures from the distributional assumptions, alternative models 
will be explored using appropriate transformed data. 
Model Results Presentation 
• 
Geometric mean and 90% CIs will be calculated for each of the ethnic cohorts. 
• 
Comparisons for Japanese/Caucasians and Chinese/Caucasians will also be presented 
– this will be determined as differences on the loge scale back transformed to present 
as ratios.  
 
4.2.2. 
Safety 
The following primary safety endpoints will be summarised descriptively by ethnic 
cohort and treatment group, as described in Section 4.5:  
• 
Incidence of adverse events (AEs)  
• 
Serious adverse events (SAEs)  
• 
Withdrawals due to AEs  


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• 
Occurrence of clinically important changes from baseline in clinical laboratory 
parameters, vital signs and ECGs 
 
4.2.3. 
Sensitivity analyses 
No formal sensitivity analyses are planned.  
 
4.3. 
Secondary Endpoint(s) Analyses 
The secondary endpoints for this study are: 
• 
Reduction (%) from baseline in free CCL17: maximum, minimum and at Days 7, 14, 
28 and 56 post-dose 
• 
Total CCL17 (free and when bound to GSK3858279): maximum observed 
concentration (Cmax), time of Cmax (tmax), maximum fold increase compared to 
baseline, fold increase compared to baseline at Days 7, 14, 28 and 56 post-dose. 
• 
Incidence of pre-existing ADAs 
• 
Incidence of treatment-emergent ADAs over time (and whether neutralising) 
4.3.1. 
Target Engagement 
All TE analyses will be performed on the TE population. Calculations will be based on 
the actual sampling times recorded during the study.  
Free and total CCL17 concentration-time data will be listed for each participant and 
summarized by planned time point and cohort.  
For Free CCL17, Total CCL17 and Total CCL17 Fold Increase parameters, the following 
summary statistics will be calculated for each cohort: 
• 
Geometric mean, 95% CI of the geometric mean, SD(log), median, min, and max  
For Free CCL17 Percentage Reduction parameter, the following summary statistics will 
be calculated for each cohort: 
• 
Geometric mean, 95% CI of the geometric mean, SD(logit), median, min, and max  
Individual serum concentration-time data and summary data will be graphically 
displayed.  
From the serum concentration-time data collected up to Day 57, the following target 
engagement parameters will be derived, as data permit:  


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• 
Baseline for free and total CCL17 
• 
Percentage reduction from baseline in free CCL17 by time point (Days 7, 14, 28 and 
56 post-dose)  
• 
Minimum and maximum percentage reduction from baseline in free CCL17 
• 
Cmax and tmax for total CCL17 
• 
Fold increase compared to baseline for total CCL17 by time point 
• 
Maximum fold increase compared to baseline for total CCL17  
 
4.3.1.1. 
Summary Measures of Derived Parameters 
TE parameters will be listed for each participant and summarized descriptively by cohort. 
For each of these parameters, the following summary statistics will be calculated for each 
cohort:  
• 
Median, maximum, minimum, arithmetic mean and standard deviation of non-
transformed data. 
• 
Geometric mean, 95% CI for the geometric mean, standard deviation and coefficient 
of variation of logarithmically transformed data.  
• 
Geometric mean, 95% CI for the geometric mean and standard deviation of logit 
transformed data. A logit-transformation will be used for the percentage reduction 
(including minimum and maximum) parameter. 
 
For tmax, arithmetic mean, standard deviation, median, maximum and minimum will be 
calculated. 
4.3.2. 
Anti-drug antibody (ADA) formation  
The incidence of pre-existing ADAs and the incidence of treatment-emergent ADAs over 
time (and whether neutralising) will be summarised descriptively. 
 
4.3.3. 
Sensitivity analyses 
No formal sensitivity analyses are planned.  
 
4.4. 
Exploratory Endpoint Analyses 
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4.5. 
Safety Analyses 
The safety analyses will be based on the Safety Analysis Set, unless otherwise specified. 
Safety data will be presented by ethnic cohort and treatment group.  
4.5.1. 
Adverse Events  
An adverse event (AE) is considered study intervention emergent if the AE onset date is 
on or after study intervention start date. All AE summaries will be based on study 
intervention emergent events unless otherwise specified. SAE summaries will be based 
on all SAEs reported regardless of whether they meet the definition of study intervention 
emergent or not. All AE and SAE summaries will be by preferred term (PT) and System 
Organ Class (SOC). 
Adverse events will be coded using the standard Medical Dictionary for Regulatory 
Affairs (MedDRA dictionary).  
An overview summary of AEs, including counts and percentages of participants with any 
AE, AEs related to study intervention, mild, moderate, or severe AEs, SAEs, SAEs 
related to study intervention, fatal SAEs, and fatal SAEs related to study intervention will 
be produced. 
A separate summary will be provided for study intervention-related AEs. A study 
intervention-related AE is defined as an AE for which the investigator classifies the 
possible relationship to study intervention as “Yes”. A worst-case scenario approach will 
be taken to handle missing relatedness data, i.e. the summary table will include events 
with the relationship to study intervention as ‘Yes’ or missing.  
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All SAEs will be tabulated based on the number and percentage of participants who 
experienced the event. Separate summaries will also be provided for study intervention-
related SAEs.  
4.5.1.1. 
Adverse Events of Special Interest 
There are no adverse events of special interest identified for this study. 
 
4.5.1.2. 
COVID-19 Assessment and COVID-19 AEs 
A standardized MedDRA Query (SMQ) will be used to identify all COVID-19 AEs. 
The incidence of AEs and SAEs of COVID-19, COVID-19 AEs leading to study 
intervention discontinuation, COVID-19 AEs leading to study withdrawal, and severe 
COVID-19 AEs at individual PT level can be obtained from the standard AE/SAE 
summaries. 
COVID-19 assessments for participants with COVID-19 AEs will be summarized.  
If >25% participants in any given cohort report ≥1 COVID-19 AE, then onset and 
duration of the first occurrence of COVID-19 AEs, and COVID-19 AE symptoms (from 
the COVID-19 eCRF page) will be summarized. The same rule will apply to COVID-19 
SAEs. 
4.5.2. 
Additional Safety Assessments 
4.5.2.1. 
Laboratory Data 
Summaries of worst-case changes from baseline with respect to Potential Clinical 
Importance (PCI) Criteria will be generated. Decreases to low, changes to normal or no 
changes from baseline, and increases to high will be summarized for the worst-case post-
baseline. If a subject has a decrease to low and an increase to high during the same time 
interval, then the subject is counted in both the “Decrease to Low” categories and the 
“Increase to High” categories.  
Separate summary tables for haematology, and chemistry laboratory tests will be 
produced. Liver function laboratory tests will be included with chemistry lab tests. 
4.5.2.2. 
Vital Signs 
A summary of change from baseline vital sign values will be provided by visit and 
treatment group, including systolic blood pressure, diastolic blood pressure, heart rate and 
temperature. 
Summaries of vital sign results relative to PCI criteria will also be provided. The 
summary will include baseline, planned visit and worst-case post baseline. 


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4.5.2.3. 
ECG 
The baseline ECG will be taken as the mean of the triplicate values collected pre-dose on 
Day 1. The following will be summarised by visit: ECG findings and change from 
baseline in ECG values. 
The number of subjects with maximum QTc values at baseline and post-baseline relative 
to baseline will be summarized using the following categories: No Change or Decrease 
To <=450, Any Increase >450, Increase To >450 to <=480, Increase To >480 to <=500, 
and Increase To >500. 
The changes in QTc values will be categorized into the clinical concern ranges which are 
specific to changes in QTc: Increase of <= 30, 31-60 and >60 msec. A summary of 
change in QTc value will display the number and percentage of subjects with a change 
within each range for the worst-case post-baseline only. Subjects with missing baseline 
values will be excluded from this summary. 
 
4.6. 
Other Analyses 
4.6.1. 
Subgroup analyses 
No formal subgroup analyses are planned. 
 
4.7. 
Interim Analyses 
The GSK Biostatistics Team (including Third Party Suppliers) and GSK CPMS Team 
(including Third Party Suppliers) will be unblinded to all subjects already randomised at 
the time of the interim analyses and will process and analyse the data. 
Results (group summaries and if required, individual summaries) may be shared 
internally within GSK as deemed necessary to inform the clinical development plan and 
prepare supporting documents for the potential phase 2 study. Data from the interim 
analyses may also be shared externally with regulators (e.g., via an interim CSR) as 
required to support the potential phase 2 study. 
Until the time of the primary PK and TE analysis (all participants completed Day 57), 
access to the results for interim analyses conducted at an earlier timepoint (excluding 
CPMS and Biostatistics) will be documented in a separate document which will detail the 
individuals or groups within GSK who reviewed the data (i.e. name and function, type of 
data, purpose and date). This document will be stored in the TMF. 
No changes to the conduct of the study will be implemented as a result of the interim 
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4.7.1. 
Day 57 Analysis 
Alongside the primary PK and TE analysis, an interim analysis of safety data will occur 
once all participants have completed Day 57. The planned interim analyses will be 
performed as detailed in Section 4.5 with the full list of outputs being produced specified 
in the OPS. 
This data will be assessed in an unblinded manner and used to support regulatory 
submissions. No changes to the conduct of the study will be implemented as a result of 
the interim analyses.  
As the primary purpose of the interim analyses is to provide safety data alongside 
primary PK data to regulators – to support China and Japan’s potential participation in 
GSK3858279’s phase 2 programs – data at both an individual and aggregate treatment 
group level will be provided. 
4.7.2. 
Other 
Prior to the primary PK and TE analysis, an additional interim analysis including Study 
Population, Safety, TE and PK data may be performed to support regulatory submissions. 
The data will be assessed in an unblinded manner. No changes to the conduct of the study 
will be implemented as a result of the interim analyses.  
This interim analysis will occur on all available data at a specified timepoint. This 
timepoint will be decided by the central study team in conjunction with the Chinese and 
Japanese LOCs.  
As the primary purpose of the interim analyses is to provide Safety and PK data to 
regulators – to support China and Japan’s potential participation in GSK3858279’s phase 
2 programs – data at both an individual and aggregate treatment group level will be 
provided. 
The full list of outputs being produced by the GSK Biostatistics Team (including Third 
Party Suppliers) for inclusion in this interim analysis are detailed in the OPS. GSK 
CPMS Team (including Third Party Suppliers) will produce additional outputs as 
appropriate. 
4.8. 
Changes to Protocol Defined Analyses 
The protocol specified that interim analysis details, including what data will be reviewed, 
the level of unblinding and who will have access to the data, would be documented in an 
interim charter. This information has been included in Section 4.7 and a separate interim 
analysis charter will not be produced. 
Changes from the originally planned statistical analysis specified in the protocol are 
detailed in Table 2 


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Table 2 
Changes to Protocol Defined Analysis Plan 
Protocol Defined Analysis 
SAP Defined Analysis 
Rationale for Changes 
Section 9.2.3: “Primary analysis 
will be performed on the PK 
parameters AUC (0-56) post-dose 
and Cmax. The parameters will 
be loge transformed and then 
analysed using a mixed model, 
with ethnicity and body weight 
included as covariates. Geometric 
mean and 90% confidence 
intervals will be calculated for 
each of the ethnic cohorts, along 
with the comparisons for 
Japanese/Caucasians and 
Chinese/Caucasians.” 
Section 4.2.1.2: “The PK 
parameters will be loge 
transformed and analysed 
using a mixed model. Terms 
fitted in the model will 
include ethnicity and 
loge(body weight). An 
additional model including 
the ethnicity term only will 
be fitted.” 
• 
Inclusion of additional 
analysis without body 
weight to be presented 
alongside the original 
model  
• 
Inclusion of 
loge(bodyweight) instead 
of bodyweight as linear 
relationship expected 
between PK parameters 
and loge (bodyweight) 
5. 
SAMPLE SIZE DETERMINATION 
Approximately 10 participants are to be randomized (7 active: 3 placebo) per cohort to 
ensure that a minimum of 6 participants on active and 2 on placebo per cohort are 
evaluable. An evaluable participant is one that has been dosed and has safety and all PK 
data up to Day 57. Replacements (assigned to the same treatment) are permitted at the 
discretion of the sponsor in consultation with the investigator.  
 
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6. 
SUPPORTING DOCUMENTATION 
6.1. 
Appendix 1 Study Population Analyses 
Unless otherwise specified, the study population analyses will be based on the Screened, 
Enrolled or Randomised Analysis Sets. A summary of the number of participants in each 
of the participant level analysis set will be provided. 
6.1.1. 
Participant Disposition 
A summary of the number and percentage of participants who completed the study as 
well as those who prematurely withdrew from the study will be provided. Reasons for 
study withdrawal will be summarized. For those who have neither completed nor 
withdrawn, they will be categorized as ongoing. A participant is considered to have 
completed the study if they have completed all planned study assessments including the 
follow-up visit.  
 
Rescreening of screen failures is allowed as per protocol. Rescreened participants will be 
summarized under their latest participant number. 
6.1.2. 
Demographic and Baseline Characteristics 
The demographic characteristics including age, gender, ethnicity, height/weight at 
screening, Body Mass Index (BMI) and race will be summarized with descriptive 
statistics. In addition, the following age categories will be summarized: 18-64, 65-84 and 
>=85 based on the Enrolled Analysis Set. 
6.1.3. 
Protocol Deviations 
Important protocol deviations will be summarized and include overall important protocol 
deviations, COVID-19 related important protocol deviations and non COVID-19 related 
important protocol deviations. 
Protocol deviations will be tracked by the study team throughout the conduct of the 
study. These protocol deviations will be reviewed to identify those considered as 
important as follows: 
o Data will be reviewed prior to unblinding and freezing the database to ensure all 
important deviations (where possible without knowing the study intervention 
details) are captured and categorised in the protocol deviations dataset.  
o This dataset will be the basis for the summaries of important protocol deviations. 
 
Visits and assessments missed due to the COVID-19 pandemic, together with visits 
conducted remotely, will be summarized in both a table and a figure.  


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6.1.4. 
Prior and Concomitant Medications 
Concomitant medications will be coded using both the GSK Drug and WHO Drug 
dictionaries. However, the summary will be based on GSK Drug dictionary only. The 
summary of concomitant medications will be provided by ingredient, i.e. multi-ingredient 
medications will be summarized for each individual ingredient rather than a combination 
of ingredients. The summary will be created using ingredient base names, i.e. ingredients 
with the same base name but different salt will appear under one base name in the 
summary.  
Prior medication is any medication or vaccine (including over-the-counter or prescription 
medicines, recreational drugs, vitamins, and/or herbal supplements) or other specific 
categories of interest without missing end date and with end date >7 days prior to dosing.  
Concomitant medication is any medication or vaccine (including over-the-counter or 
prescription medicines, recreational drugs, vitamins, and/or herbal supplements) or other 
specific categories of interest, that is not considered prior.  
 
6.1.5. 
Additional Analyses Due to the COVID-19 Pandemic 
A participant is defined as having a suspected, probable or confirmed COVID-19 
infection during the study if the answer is “Confirmed”, “Probable” or “Suspected” to the 
case diagnosis question from the COVID-19 coronavirus infection assessment eCRF. 
Numbers of participants with a suspected, probable or confirmed COVID-19 infection, 
and of COVID-19 test results will be summarized. 


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6.2. 
Appendix 2 Data Derivations Rule 
6.2.1. 
Criteria for Potential Clinical Importance 
6.2.1.1. 
Vital Signs 
Vital Sign Parameter 
(Absolute) 
Units 
Clinical Concern Range 
Lower 
Upper 
Systolic Blood Pressure 
mmHg 
< 85 
> 160 
Diastolic Blood Pressure 
mmHg 
< 45 
> 100 
Heart Rate 
bpm 
< 40 
> 110 
Body Temperature 
°C 
≤ 35.5 
>38.0 
6.2.1.2. 
Laboratory Values 
Haematology 
Laboratory Parameter 
 
Units 
Category 
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Hematocrit  
Ratio of 
1 
Male 
0.39 
0.54 
Female 
0.35 
0.49 
∆ from BL ↓0.075 
 
Hemoglobin  
g/L 
 
Male 
124 
180 
Female 
109 
180 
∆ from BL ↓25 
 
Lymphocytes  
x109/ L 
 
0.75 
 
Neutrophil Count  
x109/ L 
 
1.5 
 
Platelet Count  
x109/ L 
 
100 
550 
White Blood Cell Count (WBC) 
x109/ L 
 
2.5 
20 
 
Clinical Chemistry 
Laboratory Parameter 
Units 
Category 
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Albumin  
g/L 
 
30 
 
Calcium 
mmol/L 
 
2 
2.75 
Creatinine 
umol/L 
 
 
1.3 X ULN 
Creatinine 
umol/L 
∆ from BL 
 
↑ 44.2 
Glucose 
mmol/L 
 
3 
9 
Potassium 
mmol/L 
 
3 
5.5 
Sodium 
mmol/L 
 
130 
150 
Total CO2 
mmol/L 
 
18 
32 
Creatinine Kinase 
mg/dL 
 
 
>1.6 X ULN 
C-reactive Protein 
mg/L 
 
 
≥3.0 
Troponin T 
ng/ml 
 
 
14.1 
NT-pro BNP 
ng/L 
 
 
125.99 
 
Urinalysis 
A subject is considered to have urinalysis results of PCI, if they have abnormal microscopic examination.  


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XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021 
Liver Function 
Test Analyte 
Units 
Category 
Clinical Concern Range 
ALT/SGPT  
IU/L 
High 
≥2xULN 
AST/SGOT  
IU/L 
High 
≥2xULN 
AlkPhos  
IU/L 
High 
≥2xULN 
T Bilirubin  
µmol/L 
High 
≥1.5xULN 
T. Bilirubin + ALT 
µmol/L 
High 
ALT≥3xULN AND bilirubin≥ 1.5xULN 
IU/L 
6.2.1.3. 
ECG 
ECG Parameter 
Units 
Clinical Concern Range 
Lower 
Upper 
Absolute 
Absolute QTc Interval 
msec 
 
>500 
Absolute PR Interval 
msec 
<110 
>220  
Absolute QRS Interval 
msec 
<75 
>120 
Change from Baseline 
Increase from Baseline QTc msec 
 
>60 
6.2.2. 
Study Phase 
Assessments and events will be classified according to the time of occurrence relative to 
the study intervention period.  
Pre-Intervention is defined as time prior to the single dose of study intervention. 
On-Intervention is defined as time following single dose. If time of assessment (e.g. 
ECG, Lab, vital signs) is not collected and assessment date is the same as the dose date, 
the assessment is considered pre-intervention.  If time of study intervention (e.g. AE, 
concomitant medication) is not collected and the start/end date is the same as dose date, it 
is considered on-intervention. 
6.2.3. 
Study Day and Reference Dates 
The safety reference date is the study intervention start date and will be used to calculate 
study day for safety measures.  
The study day is calculated as below: 
Assessment Date = Missing              → Study Day = Missing  
Assessment Date < Reference Date → Study Day = Assessment Date – Ref Date 
Assessment Date ≥ Reference Date → Study Day = Assessment Date – Ref Date + 1     
 


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XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021 
6.2.4. 
Assessment Window  
For data summaries by visit, scheduled visits with nominal visit description as well as the 
worst-case post baseline will be displayed. Unscheduled visits will not be displayed or 
slotted into a visit window but will be included in the derivation of worst-case post 
baseline assessment. All unscheduled visits will be displayed in the listing. 
6.2.5. 
Multiple measurements at One Analysis Time Point 
When triplicate ECG assessments are taken, mean of the measurement will be calculated 
first and summary statistics will be based on the calculated mean. This will apply to both 
baseline and post baseline assessments. 
6.2.6. 
Handling of Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays.   
• 
However, where necessary, display macros may impute dates as temporary 
variables for sorting data in listings only. In addition, partial dates may be 
imputed for ‘slotting’ data to study phases or for specific analysis purposes as 
outlined below. 
• 
Imputed partial dates will not be used to derive study day, time to onset or 
duration (e.g., time to onset or duration of adverse events), or elapsed time 
variables (e.g., time since diagnosis).  
Adverse 
Events 
• 
Partial dates for AE recorded in the CRF will be imputed using the following 
conventions: 
Missing start 
day 
If study intervention start date is missing (i.e. participant 
did not start study intervention), then set start date = 1st 
of month. 
Else if study intervention start date is not missing: 
o If month and year of start date = month and year 
of study intervention start date, then 
▪ 
If stop date contains a full date and stop 
date is earlier than study intervention 
start date, then set start date= 1st of 
month. 
▪ 
Else set start date = study intervention 
start date. 
Else set start date = 1st of month. 
Missing start 
day and month 
If study intervention start date is missing (i.e. participant 
did not start study intervention), then set start date = 


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XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021 
Element 
Reporting Detail 
January 1. 
Else if study intervention start date is not missing: 
o If year of start date = year of study intervention 
start date, then 
▪ 
If stop date contains a full date and 
stop date is earlier than study 
intervention start date, then set start 
date = January 1. 
▪ 
Else set start date = study 
intervention start date.       
Else set start date = January 1. 
Missing end day  A '28/29/30/31' will be used for the day (dependent on 
the month and year). 
Missing end day 
and month 
No Imputation 
Completely 
missing 
start/end date 
No imputation 
Concomitant 
Medications/
Medical 
History 
• 
Partial dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
 
Missing start 
day 
If study intervention start date is missing (i.e. 
participant did not start study intervention), then set 
start date = 1st of month. 
Else if study intervention start date is not missing: 
o If month and year of start date = month and 
year of study intervention start date, then 
▪ If stop date contains a full date and stop 
date is earlier than study intervention 
start date, then set start date= 1st of 
month. 
▪ Else set start date = study intervention 
start date. 
Else set start date = 1st of month. 
Missing start 
If study intervention start date is missing (i.e. 


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XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021 
Element 
Reporting Detail 
day and month 
participant did not start study intervention), then set 
start date = January 1. 
Else if study intervention start date is not missing: 
o If year of start date = year of study intervention 
start date, then 
▪ 
If stop date contains a full date and stop 
date is earlier than study intervention 
start date, then set start date = January 
1. 
▪ 
Else set start date = study. intervention 
start date.       
Else set start date = January 1. 
Missing end day 
A '28/29/30/31' will be used for the day (dependent on 
the month and year).  
Missing end day 
and month 
A '31' will be used for the day and 'Dec' will be used for 
the month. 
Completely 
missing start/end 
date 
No imputation 
 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
None 
 
NONMEM 
 
 
WinNonlin 


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7. 
REFERENCES 
GlaxoSmithKline Document Number TMF-14343601. Project Data Analysis Plan for an 
Integrated Analysis of GSK3858279 Pharmacokinetic/Target 
Engagement/Pharmacodynamic relationship in Healthy Participants, Participants with 
Osteoarthritis of the Knee and other Indications. Effective Date 30-Dec-2021