Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics and Antiviral Activity of IONIS-HBVRx in Treatment-Naïve Patients With Chronic HBV Infection (NCT NCT02981602)

Last Updated: 2021-08-10

Results Overview

An adverse event is any unfavorable and unintended sign (including a clinically-significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. Any adverse event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any important medical event according to medical judgment were categorized as SAE.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Up to Day 211

Results posted on

2021-08-10

Participant Flow

This study evaluated safety, tolerability, pharmacokinetics and antiviral activity of GSK3228836 in two population of participants with Chronic Hepatitis B (CHB) virus infection: treatment-naive participants (Cohorts 1, 2 and 3) and participants on stable nucleos(t)ide treatment (Cohort 4)

A total of 31 participants were enrolled and received either GSK3228836 or placebo. In Cohort 3 participants were administered GSK3228836 300 milligram \[mg\] instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Participant milestones

Participant milestones
Measure	Cohort 1 GSK3228836 150 mg Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 GSK3228836 300 mg Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.
Overall Study STARTED	6	12	6	5	2
Overall Study COMPLETED	6	12	6	4	2
Overall Study NOT COMPLETED	0	0	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 GSK3228836 150 mg Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 GSK3228836 300 mg Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.
Overall Study Adverse Event	0	0	0	1	0

Baseline Characteristics

Safety, Tolerability, Pharmacokinetics and Antiviral Activity of IONIS-HBVRx in Treatment-Naïve Patients With Chronic HBV Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Total n=31 Participants Total of all reporting groups
Age, Continuous	42.5 Years STANDARD_DEVIATION 11.22 • n=5 Participants	42.6 Years STANDARD_DEVIATION 14.12 • n=7 Participants	49.3 Years STANDARD_DEVIATION 12.66 • n=5 Participants	48.4 Years STANDARD_DEVIATION 7.40 • n=4 Participants	37.0 Years STANDARD_DEVIATION 2.83 • n=21 Participants	44.5 Years STANDARD_DEVIATION 11.90 • n=10 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	15 Participants n=10 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	1 Participants n=21 Participants	16 Participants n=10 Participants
Race/Ethnicity, Customized Race · Asian	6 Participants n=5 Participants	12 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	2 Participants n=21 Participants	31 Participants n=10 Participants

PRIMARY outcome

Timeframe: Up to Day 211

Population: Safety Population includes all randomized participants who received at least 1 dose of GSK3228836 or placebo. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=5%) Non-SAE (>=5%)	3 Participants	0 Participants	6 Participants	5 Participants	2 Participants
Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=5%) SAE	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Blood samples were collected for the analysis of clinical parameters including ALT, ALP, CK, GGT, LDH and AST. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time ALT, Day57, n= 5,12,6,4,2	46.0 Units per liter (U/L) Standard Deviation 42.31	1.0 Units per liter (U/L) Standard Deviation 3.54	37.5 Units per liter (U/L) Standard Deviation 58.31	45.6 Units per liter (U/L) Standard Deviation 60.06	-2.2 Units per liter (U/L) Standard Deviation 8.77
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time AST, Day57, n= 5,12,6,4,2	18.3 Units per liter (U/L) Standard Deviation 15.84	4.5 Units per liter (U/L) Standard Deviation 2.12	23.3 Units per liter (U/L) Standard Deviation 50.25	22.8 Units per liter (U/L) Standard Deviation 34.30	2.3 Units per liter (U/L) Standard Deviation 3.33
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time AST, Day85, n= 6,12,6,4,2	5.5 Units per liter (U/L) Standard Deviation 4.51	3.0 Units per liter (U/L) Standard Deviation 0.00	4.6 Units per liter (U/L) Standard Deviation 20.37	3.0 Units per liter (U/L) Standard Deviation 16.66	1.5 Units per liter (U/L) Standard Deviation 4.46
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time CK, Day29, n= 6,12,6,4,2	-6.8 Units per liter (U/L) Standard Deviation 19.21	49.0 Units per liter (U/L) Standard Deviation 62.23	-17.6 Units per liter (U/L) Standard Deviation 28.46	35.5 Units per liter (U/L) Standard Deviation 127.87	-13.2 Units per liter (U/L) Standard Deviation 29.36
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time CK, Day85, n= 6,12,6,4,2	178.8 Units per liter (U/L) Standard Deviation 359.38	26.5 Units per liter (U/L) Standard Deviation 31.82	16.8 Units per liter (U/L) Standard Deviation 28.51	26.2 Units per liter (U/L) Standard Deviation 61.64	5.0 Units per liter (U/L) Standard Deviation 49.78
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time GGT, Day85, n= 6,12,6,4,2	5.3 Units per liter (U/L) Standard Deviation 3.10	1.0 Units per liter (U/L) Standard Deviation 2.83	3.2 Units per liter (U/L) Standard Deviation 6.66	-0.5 Units per liter (U/L) Standard Deviation 1.52	-17.5 Units per liter (U/L) Standard Deviation 37.56
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time LDH, Day29, n= 6,12,6,4,2	46.8 Units per liter (U/L) Standard Deviation 35.51	12.5 Units per liter (U/L) Standard Deviation 0.71	1.7 Units per liter (U/L) Standard Deviation 41.09	12.0 Units per liter (U/L) Standard Deviation 27.03	-1.5 Units per liter (U/L) Standard Deviation 15.00
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time ALT, Day29, n= 6,12,6,4,2	45.3 Units per liter (U/L) Standard Deviation 32.10	-0.5 Units per liter (U/L) Standard Deviation 3.54	52.5 Units per liter (U/L) Standard Deviation 112.14	15.7 Units per liter (U/L) Standard Deviation 56.65	-0.7 Units per liter (U/L) Standard Deviation 8.91
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time ALT, Day85, n= 6,12,6,4,2	7.5 Units per liter (U/L) Standard Deviation 13.18	-0.5 Units per liter (U/L) Standard Deviation 0.71	8.8 Units per liter (U/L) Standard Deviation 29.87	-10.5 Units per liter (U/L) Standard Deviation 30.20	0.5 Units per liter (U/L) Standard Deviation 9.14
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time ALT, Day211, n= 6,12,6,4,2	6.5 Units per liter (U/L) Standard Deviation 9.95	5.5 Units per liter (U/L) Standard Deviation 3.54	-16.2 Units per liter (U/L) Standard Deviation 30.75	-24.3 Units per liter (U/L) Standard Deviation 43.68	-3.2 Units per liter (U/L) Standard Deviation 12.88
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time ALP, Day29, n= 6,12,6,4,2	9.8 Units per liter (U/L) Standard Deviation 11.95	0.0 Units per liter (U/L) Standard Deviation 0.90	5.2 Units per liter (U/L) Standard Deviation 14.60	-3.2 Units per liter (U/L) Standard Deviation 8.23	-0.7 Units per liter (U/L) Standard Deviation 8.12
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time ALP, Day57, n= 5,12,6,4,2	1.3 Units per liter (U/L) Standard Deviation 9.22	4.0 Units per liter (U/L) Standard Deviation 5.66	13.3 Units per liter (U/L) Standard Deviation 14.55	7.8 Units per liter (U/L) Standard Deviation 12.09	8.0 Units per liter (U/L) Standard Deviation 11.31
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time ALP, Day85, n= 6,12,6,4,2	0.0 Units per liter (U/L) Standard Deviation 4.24	6.0 Units per liter (U/L) Standard Deviation 4.24	9.9 Units per liter (U/L) Standard Deviation 9.24	7.2 Units per liter (U/L) Standard Deviation 7.73	7.7 Units per liter (U/L) Standard Deviation 9.89
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time ALP, Day211, n= 6,12,6,4,2	1.5 Units per liter (U/L) Standard Deviation 7.85	5.0 Units per liter (U/L) Standard Deviation 11.31	11.3 Units per liter (U/L) Standard Deviation 13.61	18.2 Units per liter (U/L) Standard Deviation 10.32	9.3 Units per liter (U/L) Standard Deviation 8.71
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time AST, Day29, n= 6,12,6,4,2	27.5 Units per liter (U/L) Standard Deviation 23.07	2.0 Units per liter (U/L) Standard Deviation 1.41	31.0 Units per liter (U/L) Standard Deviation 78.95	17.7 Units per liter (U/L) Standard Deviation 50.41	-0.5 Units per liter (U/L) Standard Deviation 3.99
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time AST, Day211, n= 6,12,6,4,2	5.3 Units per liter (U/L) Standard Deviation 3.30	4.5 Units per liter (U/L) Standard Deviation 2.12	-6.5 Units per liter (U/L) Standard Deviation 16.46	-9.3 Units per liter (U/L) Standard Deviation 22.20	3.8 Units per liter (U/L) Standard Deviation 3.76
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time CK, Day57, n= 5,12,6,4,2	57.0 Units per liter (U/L) Standard Deviation 142.54	111.0 Units per liter (U/L) Standard Deviation 148.49	9.8 Units per liter (U/L) Standard Deviation 25.89	-9.6 Units per liter (U/L) Standard Deviation 47.77	-0.5 Units per liter (U/L) Standard Deviation 24.04
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time CK, Day211, n= 6,12,6,4,2	53.8 Units per liter (U/L) Standard Deviation 50.68	94.0 Units per liter (U/L) Standard Deviation 114.55	24.2 Units per liter (U/L) Standard Deviation 42.39	29.2 Units per liter (U/L) Standard Deviation 71.04	77.2 Units per liter (U/L) Standard Deviation 132.59
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time GGT, Day29, n= 6,12,6,4,2	5.3 Units per liter (U/L) Standard Deviation 6.70	-2.5 Units per liter (U/L) Standard Deviation 2.12	3.1 Units per liter (U/L) Standard Deviation 8.27	-2.3 Units per liter (U/L) Standard Deviation 3.88	-11.7 Units per liter (U/L) Standard Deviation 22.27
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time GGT, Day57, n= 5,12,6,4,2	9.0 Units per liter (U/L) Standard Deviation 3.74	2.0 Units per liter (U/L) Standard Deviation 2.83	6.5 Units per liter (U/L) Standard Deviation 15.85	1.4 Units per liter (U/L) Standard Deviation 3.44	-17.0 Units per liter (U/L) Standard Deviation 36.30
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time GGT, Day211, n= 6,12,6,4,2	4.3 Units per liter (U/L) Standard Deviation 2.22	2.0 Units per liter (U/L) Standard Deviation 1.41	-1.1 Units per liter (U/L) Standard Deviation 2.15	-7.7 Units per liter (U/L) Standard Deviation 11.57	-17.8 Units per liter (U/L) Standard Deviation 41.06
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time LDH, Day57, n= 5,12,6,4,2	4.8 Units per liter (U/L) Standard Deviation 9.25	11.0 Units per liter (U/L) Standard Deviation 11.31	-4.7 Units per liter (U/L) Standard Deviation 21.40	4.4 Units per liter (U/L) Standard Deviation 26.68	22.0 Units per liter (U/L) Standard Deviation 36.74
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time LDH, Day85, n= 6,12,6,4,2	3.8 Units per liter (U/L) Standard Deviation 17.19	6.0 Units per liter (U/L) Standard Deviation 8.49	-12.3 Units per liter (U/L) Standard Deviation 22.42	9.5 Units per liter (U/L) Standard Deviation 22.79	29.2 Units per liter (U/L) Standard Deviation 35.29
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma-glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Over Time LDH, Day211, n= 6,12,6,4,2	25.3 Units per liter (U/L) Standard Deviation 13.60	24.0 Units per liter (U/L) Standard Deviation 22.63	3.3 Units per liter (U/L) Standard Deviation 28.06	7.0 Units per liter (U/L) Standard Deviation 18.78	55.0 Units per liter (U/L) Standard Deviation 54.59

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Population: Safety population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Blood samples were collected for the analysis of clinical chemistry parameter-albumin and total protein. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time Albumin, Day85, n= 6,12,6,4,2	1.3 Grams per liter Standard Deviation 2.22	3.0 Grams per liter Standard Deviation 2.83	2.0 Grams per liter Standard Deviation 3.28	0.0 Grams per liter Standard Deviation 2.00	-0.8 Grams per liter Standard Deviation 3.19
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time Albumin, Day211, n= 6,12,6,4,2	4.3 Grams per liter Standard Deviation 0.50	3.0 Grams per liter Standard Deviation 5.66	3.3 Grams per liter Standard Deviation 2.26	1.0 Grams per liter Standard Deviation 2.28	0.7 Grams per liter Standard Deviation 3.01
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time Total Protein, Day29, n= 6,12,6,4,2	6.5 Grams per liter Standard Deviation 3.11	1.5 Grams per liter Standard Deviation 7.78	1.9 Grams per liter Standard Deviation 3.18	-1.8 Grams per liter Standard Deviation 2.64	-1.8 Grams per liter Standard Deviation 4.75
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time Albumin, Day29, n= 6,12,6,4,2	3.0 Grams per liter Standard Deviation 2.16	1.5 Grams per liter Standard Deviation 3.54	0.3 Grams per liter Standard Deviation 2.23	-0.8 Grams per liter Standard Deviation 1.47	-1.3 Grams per liter Standard Deviation 1.51
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time Albumin, Day57, n= 5,12,6,4,2	1.8 Grams per liter Standard Deviation 1.50	5.5 Grams per liter Standard Deviation 0.71	1.7 Grams per liter Standard Deviation 2.57	0.6 Grams per liter Standard Deviation 1.67	0.0 Grams per liter Standard Deviation 1.55
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time Total Protein, Day57, n= 5,12,6,4,2	3.0 Grams per liter Standard Deviation 1.41	6.0 Grams per liter Standard Deviation 0.0	3.8 Grams per liter Standard Deviation 4.27	0.8 Grams per liter Standard Deviation 3.49	0.2 Grams per liter Standard Deviation 3.25
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time Total Protein, Day85, n= 6,12,6,4,2	3.5 Grams per liter Standard Deviation 3.42	4.5 Grams per liter Standard Deviation 2.12	3.3 Grams per liter Standard Deviation 5.03	0.8 Grams per liter Standard Deviation 3.54	0.3 Grams per liter Standard Deviation 4.97
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein Over Time Total Protein, Day211, n= 6,12,6,4,2	8.0 Grams per liter Standard Deviation 2.71	4.5 Grams per liter Standard Deviation 12.02	5.1 Grams per liter Standard Deviation 4.23	2.5 Grams per liter Standard Deviation 4.81	1.7 Grams per liter Standard Deviation 3.33

PRIMARY outcome

Timeframe: Outcome Measure Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Blood samples were collected for the analysis of clinical parameters including sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate, glucose, blood urea nitrogen (BUN), cholesterol and urate. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Bicarbonate, Day29, n= 6,12,6,4,2	0.0 Millimoles per liter Standard Deviation 2.16	-2.0 Millimoles per liter Standard Deviation 2.83	0.2 Millimoles per liter Standard Deviation 1.11	0.3 Millimoles per liter Standard Deviation 1.21	1.0 Millimoles per liter Standard Deviation 1.41
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Bicarbonate, Day211, n= 6,12,6,4,2	-0.8 Millimoles per liter Standard Deviation 2.22	-2.0 Millimoles per liter Standard Deviation 4.24	-1.0 Millimoles per liter Standard Deviation 1.81	2.8 Millimoles per liter Standard Deviation 1.94	-0.8 Millimoles per liter Standard Deviation 1.72
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Calcium, Day57, n= 5,12,6,4,2	0.013 Millimoles per liter Standard Deviation 0.0150	0.010 Millimoles per liter Standard Deviation 0.0566	0.029 Millimoles per liter Standard Deviation 0.0899	0.036 Millimoles per liter Standard Deviation 0.0658	-0.038 Millimoles per liter Standard Deviation 0.0471
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Chloride, Day57, n= 5,12,6,4,2	-1.0 Millimoles per liter Standard Deviation 0.00	-1.5 Millimoles per liter Standard Deviation 0.71	0.0 Millimoles per liter Standard Deviation 1.86	-1.2 Millimoles per liter Standard Deviation 2.17	0.7 Millimoles per liter Standard Deviation 0.82
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Chloride, Day85, n= 6,12,6,4,2	-0.3 Millimoles per liter Standard Deviation 1.50	-1.5 Millimoles per liter Standard Deviation 2.12	0.8 Millimoles per liter Standard Deviation 1.85	-1.0 Millimoles per liter Standard Deviation 2.37	1.5 Millimoles per liter Standard Deviation 1.64
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Cholesterol, Day29, n= 6,12,6,4,2	0.123 Millimoles per liter Standard Deviation 0.9238	-0.155 Millimoles per liter Standard Deviation 0.7000	-0.129 Millimoles per liter Standard Deviation 0.4305	-0.027 Millimoles per liter Standard Deviation 0.2281	-0.252 Millimoles per liter Standard Deviation 0.2044
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Cholesterol, Day57, n= 5,12,6,4,2	0.480 Millimoles per liter Standard Deviation 0.7278	0.815 Millimoles per liter Standard Deviation 0.5303	-0.328 Millimoles per liter Standard Deviation 0.8109	-0.422 Millimoles per liter Standard Deviation 0.3739	-0.717 Millimoles per liter Standard Deviation 0.5216
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Cholesterol, Day85, n= 6,12,6,4,2	0.195 Millimoles per liter Standard Deviation 0.5073	0.390 Millimoles per liter Standard Deviation 0.5091	-0.211 Millimoles per liter Standard Deviation 0.8659	-0.380 Millimoles per liter Standard Deviation 0.5772	-0.812 Millimoles per liter Standard Deviation 0.2704
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Cholesterol, Day211, n= 6,12,6,4,2	0.960 Millimoles per liter Standard Deviation 0.3982	0.360 Millimoles per liter Standard Deviation 0.7354	-0.121 Millimoles per liter Standard Deviation 0.7581	-0.110 Millimoles per liter Standard Deviation 0.4369	-0.423 Millimoles per liter Standard Deviation 0.6980
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Glucose, Day57, n= 5,12,6,4,2	0.415 Millimoles per liter Standard Deviation 1.4055	-0.360 Millimoles per liter Standard Deviation 0.1980	-0.110 Millimoles per liter Standard Deviation 1.0510	0.056 Millimoles per liter Standard Deviation 0.4161	-0.157 Millimoles per liter Standard Deviation 0.5147
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Glucose, Day85, n= 6,12,6,4,2	0.073 Millimoles per liter Standard Deviation 0.4524	-0.110 Millimoles per liter Standard Deviation 0.0000	-0.218 Millimoles per liter Standard Deviation 1.0970	0.018 Millimoles per liter Standard Deviation 0.3725	-0.315 Millimoles per liter Standard Deviation 0.2959
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Glucose, Day211, n= 6,12,6,4,2	-0.373 Millimoles per liter Standard Deviation 0.6375	-0.110 Millimoles per liter Standard Deviation 0.3111	-0.205 Millimoles per liter Standard Deviation 1.0796	0.093 Millimoles per liter Standard Deviation 0.4956	-0.223 Millimoles per liter Standard Deviation 0.5205
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Magnesium, Day29, n= 6,12,6,4,2	0.000 Millimoles per liter Standard Deviation 0.0000	0.025 Millimoles per liter Standard Deviation 0.0354	0.013 Millimoles per liter Standard Deviation 0.0377	-0.008 Millimoles per liter Standard Deviation 0.0376	-0.025 Millimoles per liter Standard Deviation 0.0524
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Magnesium, Day57, n= 5,12,6,4,2	0.013 Millimoles per liter Standard Deviation 0.0479	0.000 Millimoles per liter Standard Deviation 0.0000	0.038 Millimoles per liter Standard Deviation 0.0483	0.000 Millimoles per liter Standard Deviation 0.0500	-0.033 Millimoles per liter Standard Deviation 0.0516
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Magnesium, Day85, n= 6,12,6,4,2	-0.038 Millimoles per liter Standard Deviation 0.0479	0.000 Millimoles per liter Standard Deviation 0.0000	0.029 Millimoles per liter Standard Deviation 0.0620	-0.025 Millimoles per liter Standard Deviation 0.0612	-0.033 Millimoles per liter Standard Deviation 0.0606
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Magnesium, Day211, n= 6,12,6,4,2	0.050 Millimoles per liter Standard Deviation 0.0577	0.025 Millimoles per liter Standard Deviation 0.0354	0.042 Millimoles per liter Standard Deviation 0.0669	0.008 Millimoles per liter Standard Deviation 0.0585	-0.008 Millimoles per liter Standard Deviation 0.0492
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Phosphate, Day29, n= 6,12,6,4,2	-0.073 Millimoles per liter Standard Deviation 0.0562	-0.050 Millimoles per liter Standard Deviation 0.1131	-0.010 Millimoles per liter Standard Deviation 0.1123	0.052 Millimoles per liter Standard Deviation 0.1488	0.023 Millimoles per liter Standard Deviation 0.1472
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Phosphate, Day57, n= 5,12,6,4,2	-0.058 Millimoles per liter Standard Deviation 0.1250	-0.020 Millimoles per liter Standard Deviation 0.1556	-0.064 Millimoles per liter Standard Deviation 0.1072	0.052 Millimoles per liter Standard Deviation 0.1657	-0.025 Millimoles per liter Standard Deviation 0.1088
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Phosphate, Day85, n= 6,12,6,4,2	-0.008 Millimoles per liter Standard Deviation 0.2017	0.080 Millimoles per liter Standard Deviation 0.2546	-0.003 Millimoles per liter Standard Deviation 0.1342	-0.020 Millimoles per liter Standard Deviation 0.1942	0.055 Millimoles per liter Standard Deviation 0.1001
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Phosphate, Day211, n= 6,12,6,4,2	-0.018 Millimoles per liter Standard Deviation 0.1231	-0.130 Millimoles per liter Standard Deviation 0.1273	0.056 Millimoles per liter Standard Deviation 0.1800	0.023 Millimoles per liter Standard Deviation 0.0528	0.005 Millimoles per liter Standard Deviation 0.1401
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Potassium, Day29, n= 6,12,6,4,2	-0.05 Millimoles per liter Standard Deviation 0.289	0.00 Millimoles per liter Standard Deviation 0.141	0.16 Millimoles per liter Standard Deviation 0.215	0.08 Millimoles per liter Standard Deviation 0.248	0.12 Millimoles per liter Standard Deviation 0.458
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Potassium, Day85, n= 6,12,6,4,2	0.00 Millimoles per liter Standard Deviation 0.476	0.00 Millimoles per liter Standard Deviation 0.566	0.37 Millimoles per liter Standard Deviation 0.183	0.07 Millimoles per liter Standard Deviation 0.151	0.20 Millimoles per liter Standard Deviation 0.210
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Potassium, Day211, n= 6,12,6,4,2	0.23 Millimoles per liter Standard Deviation 0.299	0.05 Millimoles per liter Standard Deviation 0.919	0.31 Millimoles per liter Standard Deviation 0.284	0.03 Millimoles per liter Standard Deviation 0.367	0.30 Millimoles per liter Standard Deviation 0.228
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Sodium, Day29, n= 6,12,6,4,2	-1.0 Millimoles per liter Standard Deviation 2.16	-1.5 Millimoles per liter Standard Deviation 0.71	0.2 Millimoles per liter Standard Deviation 2.33	0.2 Millimoles per liter Standard Deviation 0.75	0.7 Millimoles per liter Standard Deviation 2.42
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Sodium, Day57, n= 5,12,6,4,2	-0.5 Millimoles per liter Standard Deviation 1.29	-1.0 Millimoles per liter Standard Deviation 0.00	-0.2 Millimoles per liter Standard Deviation 2.21	-1.0 Millimoles per liter Standard Deviation 1.87	-0.2 Millimoles per liter Standard Deviation 1.47
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Sodium, Day85, n= 6,12,6,4,2	-0.8 Millimoles per liter Standard Deviation 1.71	-2.0 Millimoles per liter Standard Deviation 1.41	0.5 Millimoles per liter Standard Deviation 2.28	-0.3 Millimoles per liter Standard Deviation 2.16	0.2 Millimoles per liter Standard Deviation 1.72
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Urate, Day29, n= 6,12,6,4,2	-0.0060 Millimoles per liter Standard Deviation 0.02728	0.0355 Millimoles per liter Standard Deviation 0.04172	0.0248 Millimoles per liter Standard Deviation 0.04039	0.0310 Millimoles per liter Standard Deviation 0.05007	-0.0127 Millimoles per liter Standard Deviation 0.01127
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Urate, Day57, n= 5,12,6,4,2	-0.0043 Millimoles per liter Standard Deviation 0.04377	0.0030 Millimoles per liter Standard Deviation 0.00424	0.0119 Millimoles per liter Standard Deviation 0.05856	0.0192 Millimoles per liter Standard Deviation 0.03713	-0.0158 Millimoles per liter Standard Deviation 0.02260
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Urate, Day85, n= 6,12,6,4,2	-0.0078 Millimoles per liter Standard Deviation 0.04984	0.0440 Millimoles per liter Standard Deviation 0.02121	-0.0061 Millimoles per liter Standard Deviation 0.04391	0.0168 Millimoles per liter Standard Deviation 0.04298	-0.0100 Millimoles per liter Standard Deviation 0.02592
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Urate, Day211, n= 6,12,6,4,2	0.0370 Millimoles per liter Standard Deviation 0.02599	0.0325 Millimoles per liter Standard Deviation 0.02899	-0.0005 Millimoles per liter Standard Deviation 0.05949	0.0012 Millimoles per liter Standard Deviation 0.03783	-0.0128 Millimoles per liter Standard Deviation 0.04086
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate BUN, Day29, n= 6,12,6,4,2	0.180 Millimoles per liter Standard Deviation 0.8980	0.355 Millimoles per liter Standard Deviation 1.0112	0.356 Millimoles per liter Standard Deviation 0.5040	0.417 Millimoles per liter Standard Deviation 1.0192	0.415 Millimoles per liter Standard Deviation 0.6125
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate BUN, Day85, n= 6,12,6,4,2	0.000 Millimoles per liter Standard Deviation 1.2040	0.000 Millimoles per liter Standard Deviation 0.5091	-0.059 Millimoles per liter Standard Deviation 0.8974	-0.177 Millimoles per liter Standard Deviation 0.9241	0.833 Millimoles per liter Standard Deviation 0.7011
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Bicarbonate, Day57, n= 5,12,6,4,2	0.3 Millimoles per liter Standard Deviation 2.87	-3.0 Millimoles per liter Standard Deviation 2.83	-0.1 Millimoles per liter Standard Deviation 2.02	1.0 Millimoles per liter Standard Deviation 2.65	-0.2 Millimoles per liter Standard Deviation 2.14
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Bicarbonate, Day85, n= 6,12,6,4,2	-0.8 Millimoles per liter Standard Deviation 0.50	-2.0 Millimoles per liter Standard Deviation 2.83	0.5 Millimoles per liter Standard Deviation 1.83	0.2 Millimoles per liter Standard Deviation 3.92	-0.8 Millimoles per liter Standard Deviation 0.75
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Calcium, Day29, n= 6,12,6,4,2	0.063 Millimoles per liter Standard Deviation 0.0479	-0.030 Millimoles per liter Standard Deviation 0.0707	0.015 Millimoles per liter Standard Deviation 0.0735	0.012 Millimoles per liter Standard Deviation 0.0811	-0.040 Millimoles per liter Standard Deviation 0.0506
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Calcium, Day85, n= 6,12,6,4,2	-0.013 Millimoles per liter Standard Deviation 0.0675	0.050 Millimoles per liter Standard Deviation 0.0707	0.046 Millimoles per liter Standard Deviation 0.0944	0.020 Millimoles per liter Standard Deviation 0.0672	-0.028 Millimoles per liter Standard Deviation 0.0679
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Calcium, Day211, n= 6,12,6,4,2	0.068 Millimoles per liter Standard Deviation 0.0746	-0.025 Millimoles per liter Standard Deviation 0.1344	0.056 Millimoles per liter Standard Deviation 0.0745	0.052 Millimoles per liter Standard Deviation 0.0618	-0.025 Millimoles per liter Standard Deviation 0.0789
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Chloride, Day29, n= 6,12,6,4,2	-2.0 Millimoles per liter Standard Deviation 1.83	-1.5 Millimoles per liter Standard Deviation 0.71	-0.3 Millimoles per liter Standard Deviation 1.97	-0.8 Millimoles per liter Standard Deviation 2.14	0.8 Millimoles per liter Standard Deviation 1.94
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Chloride, Day211, n= 6,12,6,4,2	-0.5 Millimoles per liter Standard Deviation 0.58	-1.0 Millimoles per liter Standard Deviation 1.41	0.0 Millimoles per liter Standard Deviation 2.30	-0.8 Millimoles per liter Standard Deviation 2.48	1.7 Millimoles per liter Standard Deviation 2.94
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Glucose, Day29, n= 6,12,6,4,2	-0.290 Millimoles per liter Standard Deviation 0.1299	0.225 Millimoles per liter Standard Deviation 0.0778	0.009 Millimoles per liter Standard Deviation 0.7782	0.170 Millimoles per liter Standard Deviation 0.7148	0.498 Millimoles per liter Standard Deviation 1.3437
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Potassium, Day57, n= 5,12,6,4,2	0.03 Millimoles per liter Standard Deviation 0.206	-0.05 Millimoles per liter Standard Deviation 0.354	0.27 Millimoles per liter Standard Deviation 0.161	0.08 Millimoles per liter Standard Deviation 0.335	0.08 Millimoles per liter Standard Deviation 0.293
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate Sodium, Day211, n= 6,12,6,4,2	0.3 Millimoles per liter Standard Deviation 0.50	-1.0 Millimoles per liter Standard Deviation 0.00	-0.3 Millimoles per liter Standard Deviation 1.96	-0.5 Millimoles per liter Standard Deviation 2.35	0.2 Millimoles per liter Standard Deviation 1.94
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate BUN, Day57, n= 5,12,6,4,2	0.980 Millimoles per liter Standard Deviation 1.5543	0.180 Millimoles per liter Standard Deviation 0.2546	0.238 Millimoles per liter Standard Deviation 0.7960	0.788 Millimoles per liter Standard Deviation 0.9903	0.535 Millimoles per liter Standard Deviation 1.1451
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphate, Glucose, Blood Urea Nitrogen, Cholesterol and Urate BUN, Day211, n= 6,12,6,4,2	0.893 Millimoles per liter Standard Deviation 1.4463	0.000 Millimoles per liter Standard Deviation 0.0000	-0.208 Millimoles per liter Standard Deviation 1.0941	0.358 Millimoles per liter Standard Deviation 1.2580	0.713 Millimoles per liter Standard Deviation 1.1510

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Blood samples were collected for the analysis of clinical chemistry parameters: direct bilirubin, total bilirubin, indirect bilirubin and creatinine. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Total Bilirubin, Day29, n= 6,12,6,4,2	-1.53 Micromoles per liter Standard Deviation 3.497	1.40 Micromoles per liter Standard Deviation 1.414	-1.07 Micromoles per liter Standard Deviation 2.529	-1.72 Micromoles per liter Standard Deviation 2.699	-1.92 Micromoles per liter Standard Deviation 2.497
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Total Bilirubin, Day57, n= 5,12,6,4,2	-0.33 Micromoles per liter Standard Deviation 3.802	3.85 Micromoles per liter Standard Deviation 6.576	-0.40 Micromoles per liter Standard Deviation 3.930	-2.14 Micromoles per liter Standard Deviation 2.105	-1.72 Micromoles per liter Standard Deviation 1.216
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Total Bilirubin, Day211, n= 6,12,6,4,2	1.00 Micromoles per liter Standard Deviation 2.432	2.75 Micromoles per liter Standard Deviation 4.738	-0.87 Micromoles per liter Standard Deviation 3.538	-0.87 Micromoles per liter Standard Deviation 2.608	0.40 Micromoles per liter Standard Deviation 5.907
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Direct Bilirubin, Day29, n= 6,12,6,4,2	0.00 Micromoles per liter Standard Deviation 0.000	0.00 Micromoles per liter Standard Deviation 0.000	-0.02 Micromoles per liter Standard Deviation 0.061	0.00 Micromoles per liter Standard Deviation 0.000	0.02 Micromoles per liter Standard Deviation 0.041
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Direct Bilirubin, Day57, n= 5,12,6,4,2	0.05 Micromoles per liter Standard Deviation 0.105	0.00 Micromoles per liter Standard Deviation 0.000	-0.02 Micromoles per liter Standard Deviation 0.061	0.00 Micromoles per liter Standard Deviation 0.000	-0.07 Micromoles per liter Standard Deviation 0.167
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Direct Bilirubin, Day85, n= 6,12,6,4,2	0.00 Micromoles per liter Standard Deviation 0.000	0.00 Micromoles per liter Standard Deviation 0.000	-0.02 Micromoles per liter Standard Deviation 0.061	0.00 Micromoles per liter Standard Deviation 0.000	-0.07 Micromoles per liter Standard Deviation 0.167
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Direct Bilirubin, Day211, n= 6,12,6,4,2	0.00 Micromoles per liter Standard Deviation 0.000	0.00 Micromoles per liter Standard Deviation 0.000	-0.02 Micromoles per liter Standard Deviation 0.061	0.00 Micromoles per liter Standard Deviation 0.000	0.05 Micromoles per liter Standard Deviation 0.122
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Indirect Bilirubin, Day29, n= 0,0,1,0,0	—	—	—	—	-0.60 Micromoles per liter Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Indirect Bilirubin, Day211, n= 0,0,1,0,0	—	—	—	—	10.50 Micromoles per liter Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Creatinine, Day29, n= 6,12,6,4,2	8.8 Micromoles per liter Standard Deviation 5.89	2.3 Micromoles per liter Standard Deviation 3.18	7.8 Micromoles per liter Standard Deviation 4.37	3.8 Micromoles per liter Standard Deviation 3.39	-0.3 Micromoles per liter Standard Deviation 7.00
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Creatinine, Day57, n= 5,12,6,4,2	2.3 Micromoles per liter Standard Deviation 12.18	2.3 Micromoles per liter Standard Deviation 9.55	5.5 Micromoles per liter Standard Deviation 6.53	2.7 Micromoles per liter Standard Deviation 5.13	2.5 Micromoles per liter Standard Deviation 5.08
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Creatinine, Day85, n= 6,12,6,4,2	2.0 Micromoles per liter Standard Deviation 5.43	2.3 Micromoles per liter Standard Deviation 3.18	3.9 Micromoles per liter Standard Deviation 6.46	0.8 Micromoles per liter Standard Deviation 8.73	1.0 Micromoles per liter Standard Deviation 5.67
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Total Bilirubin, Day85, n= 6,12,6,4,2	-0.78 Micromoles per liter Standard Deviation 2.290	5.40 Micromoles per liter Standard Deviation 7.071	-0.78 Micromoles per liter Standard Deviation 2.840	-1.47 Micromoles per liter Standard Deviation 2.151	-1.52 Micromoles per liter Standard Deviation 3.411
Change From Baseline Values in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, and Creatinine Creatinine, Day211, n= 6,12,6,4,2	2.0 Micromoles per liter Standard Deviation 5.43	6.8 Micromoles per liter Standard Deviation 3.18	4.0 Micromoles per liter Standard Deviation 8.82	0.8 Micromoles per liter Standard Deviation 6.62	4.0 Micromoles per liter Standard Deviation 6.82

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Blood samples were collected for the analysis of hematology parameters including basophil, eosinophils, WBC, lymphocytes, neutrophils, monocytes, and platelets at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Basophils, Day 29	0.0 10^9 cells per liters Standard Deviation 0.00	0.0 10^9 cells per liters Standard Deviation 0.00	0.01 10^9 cells per liters Standard Deviation 0.029	0.00 10^9 cells per liters Standard Deviation 0.000	0.00 10^9 cells per liters Standard Deviation 0.000
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Basophils, Day 57	0.0 10^9 cells per liters Standard Deviation 0.00	0.0 10^9 cells per liters Standard Deviation 0.00	0.00 10^9 cells per liters Standard Deviation 0.000	0.00 10^9 cells per liters Standard Deviation 0.000	0.00 10^9 cells per liters Standard Deviation 0.000
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Basophils, Day 85	0.0 10^9 cells per liters Standard Deviation 0.00	0.0 10^9 cells per liters Standard Deviation 0.00	0.00 10^9 cells per liters Standard Deviation 0.000	-0.02 10^9 cells per liters Standard Deviation 0.041	0.00 10^9 cells per liters Standard Deviation 0.000
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Basophils, Day 211	0.0 10^9 cells per liters Standard Deviation 0.00	0.0 10^9 cells per liters Standard Deviation 0.00	0.01 10^9 cells per liters Standard Deviation 0.029	0.00 10^9 cells per liters Standard Deviation 0.000	0.00 10^9 cells per liters Standard Deviation 0.000
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Eosinophils, Day 29	0.00 10^9 cells per liters Standard Deviation 0.082	0.00 10^9 cells per liters Standard Deviation 0.000	-0.02 10^9 cells per liters Standard Deviation 0.103	0.03 10^9 cells per liters Standard Deviation 0.103	0.03 10^9 cells per liters Standard Deviation 0.052
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Eosinophils, Day 57	0.00 10^9 cells per liters Standard Deviation 0.082	-0.10 10^9 cells per liters Standard Deviation 0.000	-0.03 10^9 cells per liters Standard Deviation 0.115	-0.02 10^9 cells per liters Standard Deviation 0.098	0.05 10^9 cells per liters Standard Deviation 0.084
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Eosinophils, Day 85	-0.03 10^9 cells per liters Standard Deviation 0.126	-0.05 10^9 cells per liters Standard Deviation 0.071	-0.03 10^9 cells per liters Standard Deviation 0.115	0.08 10^9 cells per liters Standard Deviation 0.172	0.02 10^9 cells per liters Standard Deviation 0.075
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Eosinophils, Day 211	0.05 10^9 cells per liters Standard Deviation 0.058	0.05 10^9 cells per liters Standard Deviation 0.071	-0.04 10^9 cells per liters Standard Deviation 0.108	0.10 10^9 cells per liters Standard Deviation 0.110	0.03 10^9 cells per liters Standard Deviation 0.052
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets WBC, Day 29	0.28 10^9 cells per liters Standard Deviation 0.624	-1.15 10^9 cells per liters Standard Deviation 0.212	-0.60 10^9 cells per liters Standard Deviation 0.921	-0.18 10^9 cells per liters Standard Deviation 1.206	-0.12 10^9 cells per liters Standard Deviation 0.826
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets WBC, Day 57	0.08 10^9 cells per liters Standard Deviation 0.222	-0.95 10^9 cells per liters Standard Deviation 0.636	-0.49 10^9 cells per liters Standard Deviation 0.958	-0.33 10^9 cells per liters Standard Deviation 1.172	-0.37 10^9 cells per liters Standard Deviation 1.204
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets WBC, Day 85	0.43 10^9 cells per liters Standard Deviation 0.556	-1.05 10^9 cells per liters Standard Deviation 0.071	-0.63 10^9 cells per liters Standard Deviation 0.796	-0.58 10^9 cells per liters Standard Deviation 1.177	-0.65 10^9 cells per liters Standard Deviation 0.814
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets WBC, Day 211	0.70 10^9 cells per liters Standard Deviation 0.589	-0.85 10^9 cells per liters Standard Deviation 0.212	0.01 10^9 cells per liters Standard Deviation 0.696	-0.45 10^9 cells per liters Standard Deviation 1.067	0.10 10^9 cells per liters Standard Deviation 1.834
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Lymphocytes, Day 29	-0.10 10^9 cells per liters Standard Deviation 0.216	0.20 10^9 cells per liters Standard Deviation 0.283	-0.27 10^9 cells per liters Standard Deviation 0.293	-0.10 10^9 cells per liters Standard Deviation 0.219	-0.03 10^9 cells per liters Standard Deviation 0.294
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Lymphocytes Day 57	-0.05 10^9 cells per liters Standard Deviation 0.100	-0.05 10^9 cells per liters Standard Deviation 0.071	-0.15 10^9 cells per liters Standard Deviation 0.275	0.00 10^9 cells per liters Standard Deviation 0.200	-0.10 10^9 cells per liters Standard Deviation 0.456
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Lymphocytes, Day 85	0.10 10^9 cells per liters Standard Deviation 0.294	-0.10 10^9 cells per liters Standard Deviation 0.000	-0.13 10^9 cells per liters Standard Deviation 0.273	0.17 10^9 cells per liters Standard Deviation 0.288	-0.03 10^9 cells per liters Standard Deviation 0.258
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Neutrophils, Day 57	0.13 10^9 cells per liters Standard Deviation 0.275	-0.60 10^9 cells per liters Standard Deviation 0.849	-0.31 10^9 cells per liters Standard Deviation 0.898	-0.30 10^9 cells per liters Standard Deviation 1.075	-0.32 10^9 cells per liters Standard Deviation 1.301
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Monocytes, Day 57	0.03 10^9 cells per liters Standard Deviation 0.096	-0.15 10^9 cells per liters Standard Deviation 0.354	-0.01 10^9 cells per liters Standard Deviation 0.131	0.00 10^9 cells per liters Standard Deviation 0.089	0.00 10^9 cells per liters Standard Deviation 0.167
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Monocytes, Day 85	0.03 10^9 cells per liters Standard Deviation 0.050	-0.20 10^9 cells per liters Standard Deviation 0.283	-0.04 10^9 cells per liters Standard Deviation 0.124	0.08 10^9 cells per liters Standard Deviation 0.075	0.03 10^9 cells per liters Standard Deviation 0.082
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Monocytes, Day 211	0.10 10^9 cells per liters Standard Deviation 0.115	-0.15 10^9 cells per liters Standard Deviation 0.212	-0.05 10^9 cells per liters Standard Deviation 0.100	0.07 10^9 cells per liters Standard Deviation 0.103	0.02 10^9 cells per liters Standard Deviation 0.075
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Platelets, Day 57	-7.5 10^9 cells per liters Standard Deviation 8.70	24.5 10^9 cells per liters Standard Deviation 17.68	-8.3 10^9 cells per liters Standard Deviation 31.77	-2.5 10^9 cells per liters Standard Deviation 26.76	9.7 10^9 cells per liters Standard Deviation 37.08
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Lymphocytes, Day 211	0.15 10^9 cells per liters Standard Deviation 0.208	-0.10 10^9 cells per liters Standard Deviation 0.141	-0.11 10^9 cells per liters Standard Deviation 0.334	0.17 10^9 cells per liters Standard Deviation 0.301	-0.07 10^9 cells per liters Standard Deviation 0.234
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Neutrophils, Day 29	0.30 10^9 cells per liters Standard Deviation 0.392	-1.05 10^9 cells per liters Standard Deviation 0.212	-0.36 10^9 cells per liters Standard Deviation 0.945	-0.17 10^9 cells per liters Standard Deviation 1.027	-0.17 10^9 cells per liters Standard Deviation 0.706
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Neutrophils, Day 85	0.35 10^9 cells per liters Standard Deviation 0.342	-0.65 10^9 cells per liters Standard Deviation 0.212	-0.45 10^9 cells per liters Standard Deviation 1.026	-0.95 10^9 cells per liters Standard Deviation 0.812	-0.67 10^9 cells per liters Standard Deviation 0.585
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Neutrophils, Day 211	0.48 10^9 cells per liters Standard Deviation 0.377	-0.55 10^9 cells per liters Standard Deviation 0.212	0.18 10^9 cells per liters Standard Deviation 0.725	-0.75 10^9 cells per liters Standard Deviation 0.873	0.08 10^9 cells per liters Standard Deviation 1.967
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Monocytes, Day 29	0.08 10^9 cells per liters Standard Deviation 0.050	-0.25 10^9 cells per liters Standard Deviation 0.212	-0.01 10^9 cells per liters Standard Deviation 0.138	0.08 10^9 cells per liters Standard Deviation 0.117	0.02 10^9 cells per liters Standard Deviation 0.098
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Platelets, Day 29	18.0 10^9 cells per liters Standard Deviation 32.28	16.0 10^9 cells per liters Standard Deviation 9.90	-8.3 10^9 cells per liters Standard Deviation 17.23	-0.5 10^9 cells per liters Standard Deviation 23.87	11.0 10^9 cells per liters Standard Deviation 21.94
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Platelets, Day 85	1.5 10^9 cells per liters Standard Deviation 7.14	14.5 10^9 cells per liters Standard Deviation 40.31	-8.3 10^9 cells per liters Standard Deviation 29.59	-5.2 10^9 cells per liters Standard Deviation 31.92	22.2 10^9 cells per liters Standard Deviation 27.95
Change From Baseline for Hematology Parameters: Basophils, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes, and Platelets Platelets, Day 211	17.3 10^9 cells per liters Standard Deviation 20.52	-4.5 10^9 cells per liters Standard Deviation 44.55	4.6 10^9 cells per liters Standard Deviation 43.15	12.3 10^9 cells per liters Standard Deviation 22.81	25.8 10^9 cells per liters Standard Deviation 20.49

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Population: Safety population. Only those participants with data available at the specified data points were analyzed. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Blood samples were collected for the analysis of hematology parameters including hemoglobin at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=4 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline for Hematology Parameters: Hemoglobin Day 57	-3.8 Grams per liter Standard Deviation 6.95	-3.5 Grams per liter Standard Deviation 4.95	-3.0 Grams per liter Standard Deviation 10.79	-3.3 Grams per liter Standard Deviation 10.25	-5.8 Grams per liter Standard Deviation 9.28
Change From Baseline for Hematology Parameters: Hemoglobin Day 29	-6.0 Grams per liter Standard Deviation 6.48	-11.5 Grams per liter Standard Deviation 2.12	-6.8 Grams per liter Standard Deviation 8.74	-7.3 Grams per liter Standard Deviation 3.50	-11.3 Grams per liter Standard Deviation 7.31
Change From Baseline for Hematology Parameters: Hemoglobin Day 85	-0.3 Grams per liter Standard Deviation 3.86	-5.0 Grams per liter Standard Deviation 9.90	-4.8 Grams per liter Standard Deviation 13.13	-4.0 Grams per liter Standard Deviation 10.60	-9.2 Grams per liter Standard Deviation 10.07
Change From Baseline for Hematology Parameters: Hemoglobin Day 211	4.8 Grams per liter Standard Deviation 5.19	0.0 Grams per liter Standard Deviation 1.41	1.8 Grams per liter Standard Deviation 16.68	-0.7 Grams per liter Standard Deviation 15.73	-7.5 Grams per liter Standard Deviation 6.47

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Blood samples were collected for the analysis of hematology parameter including hematocrit at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=4 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline for Hematology Parameter: Hematocrit Day 29	-2.23 Percentage of red blood cells in blood Standard Deviation 2.089	-3.30 Percentage of red blood cells in blood Standard Deviation 0.283	-2.39 Percentage of red blood cells in blood Standard Deviation 2.858	-2.47 Percentage of red blood cells in blood Standard Deviation 1.150	-4.20 Percentage of red blood cells in blood Standard Deviation 2.577
Change From Baseline for Hematology Parameter: Hematocrit Day 57	-1.10 Percentage of red blood cells in blood Standard Deviation 2.482	-0.80 Percentage of red blood cells in blood Standard Deviation 2.546	-1.04 Percentage of red blood cells in blood Standard Deviation 3.089	-1.17 Percentage of red blood cells in blood Standard Deviation 2.630	-2.17 Percentage of red blood cells in blood Standard Deviation 3.080
Change From Baseline for Hematology Parameter: Hematocrit Day 85	-0.28 Percentage of red blood cells in blood Standard Deviation 1.646	-1.65 Percentage of red blood cells in blood Standard Deviation 3.748	-0.98 Percentage of red blood cells in blood Standard Deviation 3.698	-1.33 Percentage of red blood cells in blood Standard Deviation 3.043	-3.13 Percentage of red blood cells in blood Standard Deviation 2.501
Change From Baseline for Hematology Parameter: Hematocrit Day 211	1.40 Percentage of red blood cells in blood Standard Deviation 1.930	1.05 Percentage of red blood cells in blood Standard Deviation 1.768	1.53 Percentage of red blood cells in blood Standard Deviation 4.799	-0.37 Percentage of red blood cells in blood Standard Deviation 4.065	-1.83 Percentage of red blood cells in blood Standard Deviation 2.066

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Urine samples were collected for the analysis of urine specific gravity. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value. Urine specific gravity is measured as the ratio of urine density compared with water density.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=4 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline Values in Urine Specific Gravity Day 85	0.0013 Ratio of urine to water density Standard Deviation 0.00450	0.0130 Ratio of urine to water density Standard Deviation 0.00000	0.0020 Ratio of urine to water density Standard Deviation 0.00481	-0.0007 Ratio of urine to water density Standard Deviation 0.00653	0.0057 Ratio of urine to water density Standard Deviation 0.00441
Change From Baseline Values in Urine Specific Gravity Day 211	-0.0005 Ratio of urine to water density Standard Deviation 0.00387	0.0060 Ratio of urine to water density Standard Deviation 0.00849	0.0024 Ratio of urine to water density Standard Deviation 0.00684	-0.0020 Ratio of urine to water density Standard Deviation 0.00851	0.0010 Ratio of urine to water density Standard Deviation 0.00522
Change From Baseline Values in Urine Specific Gravity Day 29	0.0028 Ratio of urine to water density Standard Deviation 0.00427	0.0080 Ratio of urine to water density Standard Deviation 0.00566	0.0033 Ratio of urine to water density Standard Deviation 0.00585	-0.0017 Ratio of urine to water density Standard Deviation 0.00703	0.0032 Ratio of urine to water density Standard Deviation 0.00523
Change From Baseline Values in Urine Specific Gravity Day 57	0.0038 Ratio of urine to water density Standard Deviation 0.00457	0.0130 Ratio of urine to water density Standard Deviation 0.00141	0.0059 Ratio of urine to water density Standard Deviation 0.00763	0.0000 Ratio of urine to water density Standard Deviation 0.00832	0.0028 Ratio of urine to water density Standard Deviation 0.00519

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Urine samples were collected for the analysis of urine albumin/creatinine ratio and urine protein/creatinine ratio. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Urine protein/creatinine ratio Day29, n=5,10,4,4,2	0.065 Milligrams per millimole Creatinine Standard Deviation 0.0238	0.025 Milligrams per millimole Creatinine Standard Deviation 0.0071	-0.002 Milligrams per millimole Creatinine Standard Deviation 0.1264	0.006 Milligrams per millimole Creatinine Standard Deviation 0.0329	-0.005 Milligrams per millimole Creatinine Standard Deviation 0.0058
Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Urine protein/creatinine ratio Day57, n=6,9,3,4,2	0.020 Milligrams per millimole Creatinine Standard Deviation 0.0000	0.010 Milligrams per millimole Creatinine Standard Deviation 0.0000	-0.043 Milligrams per millimole Creatinine Standard Deviation 0.1168	-0.007 Milligrams per millimole Creatinine Standard Deviation 0.0589	-0.003 Milligrams per millimole Creatinine Standard Deviation 0.0058
Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Urine protein/creatinine ratio Day85, n=6,8,4,3,2	0.017 Milligrams per millimole Creatinine Standard Deviation 0.0231	0.000 Milligrams per millimole Creatinine Standard Deviation 0.0141	-0.050 Milligrams per millimole Creatinine Standard Deviation 0.1042	-0.003 Milligrams per millimole Creatinine Standard Deviation 0.0554	-0.005 Milligrams per millimole Creatinine Standard Deviation 0.0129
Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Urine albumin/creatinine ratio, Day57,n=0,2,0,0,0	—	—	-10.580 Milligrams per millimole Creatinine Standard Deviation 10.9743	—	—
Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Urine protein/creatinine ratio Day211, n=4,8,4,3,1	0.013 Milligrams per millimole Creatinine Standard Deviation 0.0252	0.000 Milligrams per millimole Creatinine Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	-0.073 Milligrams per millimole Creatinine Standard Deviation 0.1235	0.003 Milligrams per millimole Creatinine Standard Deviation 0.0150	-0.005 Milligrams per millimole Creatinine Standard Deviation 0.0311
Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Urine albumin/creatinine ratio, Day29,n=0,1,0,0,0	—	—	-3.340 Milligrams per millimole Creatinine Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	—	—
Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Urine albumin/creatinine ratio, Day85,n=0,1,1,0,0	—	—	-3.480 Milligrams per millimole Creatinine Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	—	0.080 Milligrams per millimole Creatinine Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Urine samples were collected for the analysis of urine protein. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=4 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline Values in Urine Protein Day 57	4.48 Milligrams per deciliter Standard Deviation 3.502	5.56 Milligrams per deciliter Standard Deviation 3.889	5.62 Milligrams per deciliter Standard Deviation 7.910	-2.57 Milligrams per deciliter Standard Deviation 7.451	2.00 Milligrams per deciliter Standard Deviation 5.903
Change From Baseline Values in Urine Protein Day 29	11.13 Milligrams per deciliter Standard Deviation 9.288	3.76 Milligrams per deciliter Standard Deviation 5.020	7.06 Milligrams per deciliter Standard Deviation 5.130	-1.08 Milligrams per deciliter Standard Deviation 7.591	-0.51 Milligrams per deciliter Standard Deviation 2.605
Change From Baseline Values in Urine Protein Day 85	2.48 Milligrams per deciliter Standard Deviation 3.954	4.01 Milligrams per deciliter Standard Deviation 0.283	1.45 Milligrams per deciliter Standard Deviation 3.747	-2.07 Milligrams per deciliter Standard Deviation 5.814	2.29 Milligrams per deciliter Standard Deviation 2.267
Change From Baseline Values in Urine Protein Day 211	0.90 Milligrams per deciliter Standard Deviation 1.664	2.71 Milligrams per deciliter Standard Deviation 3.8250	0.90 Milligrams per deciliter Standard Deviation 2.832	-2.29 Milligrams per deciliter Standard Deviation 7.277	-0.46 Milligrams per deciliter Standard Deviation 2.214

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 23, 57, 85, 211

Blood samples were collected for the analysis of blood coagulation factors:activated partial thromboplastin time (aPTT) and Prothrombin Time (PT). Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline Values in Blood Coagulation Factors: Activated Partial Thromboplastin Time and Prothrombin Time aPTT, Day 23, n=5,11,6,4,2	-0.45 Seconds Standard Deviation 1.808	0.65 Seconds Standard Deviation 0.778	-2.33 Seconds Standard Deviation 6.460	-2.44 Seconds Standard Deviation 4.017	-1.63 Seconds Standard Deviation 1.715
Change From Baseline Values in Blood Coagulation Factors: Activated Partial Thromboplastin Time and Prothrombin Time aPTT, Day 211, n=5,11,6,2,2	1.30 Seconds Standard Deviation 4.384	2.60 Seconds Standard Deviation 3.394	-1.01 Seconds Standard Deviation 6.310	1.28 Seconds Standard Deviation 6.538	2.70 Seconds Standard Deviation 3.046
Change From Baseline Values in Blood Coagulation Factors: Activated Partial Thromboplastin Time and Prothrombin Time PT, Day 57, n=6,12,5,4,2	-0.18 Seconds Standard Deviation 0.780	0.40 Seconds Standard Deviation 0.141	-0.50 Seconds Standard Deviation 0.615	-0.10 Seconds Standard Deviation 0.740	0.20 Seconds Standard Deviation 0.869
Change From Baseline Values in Blood Coagulation Factors: Activated Partial Thromboplastin Time and Prothrombin Time aPTT, Day 57, n=6,12,5,4,2	0.13 Seconds Standard Deviation 3.627	-0.35 Seconds Standard Deviation 1.344	-3.03 Seconds Standard Deviation 5.854	1.23 Seconds Standard Deviation 3.518	-0.18 Seconds Standard Deviation 3.841
Change From Baseline Values in Blood Coagulation Factors: Activated Partial Thromboplastin Time and Prothrombin Time aPTT, Day 85, n=0,0,0,1,0	0.00 Seconds Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	—	—	—	—
Change From Baseline Values in Blood Coagulation Factors: Activated Partial Thromboplastin Time and Prothrombin Time PT, Day 23, n=5,11,6,4,2	0.33 Seconds Standard Deviation 0.585	0.60 Seconds Standard Deviation 0.141	-0.23 Seconds Standard Deviation 0.710	-0.42 Seconds Standard Deviation 0.576	0.12 Seconds Standard Deviation 0.483
Change From Baseline Values in Blood Coagulation Factors: Activated Partial Thromboplastin Time and Prothrombin Time PT, Day85, n=0,0,0,1,0	-0.80 Seconds Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	—	—	—	—
Change From Baseline Values in Blood Coagulation Factors: Activated Partial Thromboplastin Time and Prothrombin Time PT, Day211, n=5,11,6,2,2	0.45 Seconds Standard Deviation 0.919	0.70 Seconds Standard Deviation 0.283	-0.35 Seconds Standard Deviation 0.726	-0.84 Seconds Standard Deviation 0.623	0.42 Seconds Standard Deviation 0.744

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 23, 57, 85, 211

Blood samples were collected for the analysis of blood coagulation factor: Prothrombin International normalized ratio. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline Values in Blood Coagulation Factor: Prothrombin International Normalized Ratio Day 23, n=5,11,6,4,2	0.03 Ratio Standard Deviation 0.096	0.00 Ratio Standard Deviation 0.000	-0.04 Ratio Standard Deviation 0.067	-0.04 Ratio Standard Deviation 0.055	0.02 Ratio Standard Deviation 0.041
Change From Baseline Values in Blood Coagulation Factor: Prothrombin International Normalized Ratio Day 57, n=6,12,5,4,2	0.00 Ratio Standard Deviation 0.082	0.00 Ratio Standard Deviation 0.000	-0.04 Ratio Standard Deviation 0.079	-0.02 Ratio Standard Deviation 0.075	0.02 Ratio Standard Deviation 0.084
Change From Baseline Values in Blood Coagulation Factor: Prothrombin International Normalized Ratio Day 211, n=5,11,6,2,2	0.05 Ratio Standard Deviation 0.071	0.00 Ratio Standard Deviation 0.000	-0.03 Ratio Standard Deviation 0.079	-0.06 Ratio Standard Deviation 0.089	0.02 Ratio Standard Deviation 0.075
Change From Baseline Values in Blood Coagulation Factor: Prothrombin International Normalized Ratio Day 85, n=0,0,0,1,0	0.00 Ratio Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	—	—	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and up to Day 211

Population: Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Blood samples were collected from participants to evaluate change in complement C3 level at worst case post Baseline relative to Baseline. Worst case post Baseline in Complement C3 was the minimum post-Baseline level. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change in Complement C3 Level at Worst Case Post Baseline Relative to Baseline	-12.4 Milligram per deciliter Standard Deviation 3.78	-25.5 Milligram per deciliter Standard Deviation 16.26	-22.3 Milligram per deciliter Standard Deviation 12.00	-19.8 Milligram per deciliter Standard Deviation 11.72	-16.5 Milligram per deciliter Standard Deviation 13.81

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and up to Day 211

Population: Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Blood samples were collected from participants to evaluate change in complement C5a level at worst case post Baseline relative to Baseline. Worst case post Baseline in Complement C5a was the maximum post-Baseline level. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change in Complement C5a Level at Worst Case Post Baseline Relative to Baseline	2.232 Nanogram per milliliter Standard Deviation 2.2640	0.800 Nanogram per milliliter Standard Deviation 0.0000	3.778 Nanogram per milliliter Standard Deviation 6.2062	1.552 Nanogram per milliliter Standard Deviation 1.3967	1.303 Nanogram per milliliter Standard Deviation 0.8671

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and up to Day 211

Population: Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Blood samples were collected from participants to evaluate change in complement Bb level at worst case post Baseline relative to Baseline. Worst case post Baseline in Complement Bb was the maximum post-Baseline level. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change in Complement Bb Level at Worst Case Post Baseline Relative to Baseline	0.472 Microgram per milliliter Standard Deviation 0.1439	0.320 Microgram per milliliter Standard Deviation 0.3677	0.365 Microgram per milliliter Standard Deviation 0.4835	0.355 Microgram per milliliter Standard Deviation 0.1129	0.240 Microgram per milliliter Standard Deviation 0.3543

PRIMARY outcome

Timeframe: Up to Day 211

Population: Safety Population. Only those participants with data available at the specified data points were analyzed. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Female participants who were not surgically sterile or post-menopausal, underwent urine beta Human chorionic gonadotropin (Beta-HCG) pregnancy test.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=1 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=1 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=8 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=3 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=2 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Number of Participants With Reported Pregnancy	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Body temperature was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=4 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Body Temperature Day 29	0.08 Degrees Celsius Standard Deviation 0.250	0.30 Degrees Celsius Standard Deviation 0.141	-0.09 Degrees Celsius Standard Deviation 0.353	-0.05 Degrees Celsius Standard Deviation 0.288	-0.15 Degrees Celsius Standard Deviation 0.164
Change From Baseline in Body Temperature Day 57	0.48 Degrees Celsius Standard Deviation 0.096	0.20 Degrees Celsius Standard Deviation 0.849	-0.16 Degrees Celsius Standard Deviation 0.342	0.03 Degrees Celsius Standard Deviation 0.294	-0.18 Degrees Celsius Standard Deviation 0.248
Change From Baseline in Body Temperature Day 85	0.10 Degrees Celsius Standard Deviation 0.115	-0.20 Degrees Celsius Standard Deviation 0.707	-0.18 Degrees Celsius Standard Deviation 0.290	0.05 Degrees Celsius Standard Deviation 0.451	-0.13 Degrees Celsius Standard Deviation 0.103
Change From Baseline in Body Temperature Day 211	0.23 Degrees Celsius Standard Deviation 0.369	-0.10 Degrees Celsius Standard Deviation 0.424	-0.19 Degrees Celsius Standard Deviation 0.291	-0.20 Degrees Celsius Standard Deviation 0.210	-0.17 Degrees Celsius Standard Deviation 0.216

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 211

Body weight was measured at indicated time points. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=4 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Body Weight Day 57	0.20 Kilograms Standard Deviation 1.214	-0.25 Kilograms Standard Deviation 0.354	-0.10 Kilograms Standard Deviation 1.834	-0.40 Kilograms Standard Deviation 3.992	-0.18 Kilograms Standard Deviation 1.009
Change From Baseline in Body Weight Day 211	2.00 Kilograms Standard Deviation 1.212	1.95 Kilograms Standard Deviation 0.354	-0.40 Kilograms Standard Deviation 2.721	-0.15 Kilograms Standard Deviation 3.627	-0.37 Kilograms Standard Deviation 1.350
Change From Baseline in Body Weight Day 29	0.00 Kilograms Standard Deviation 0.808	-1.25 Kilograms Standard Deviation 0.636	0.20 Kilograms Standard Deviation 0.802	-0.48 Kilograms Standard Deviation 3.406	0.52 Kilograms Standard Deviation 0.786

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=4 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Diastolic Blood Pressure and Systolic Blood Pressure SBP, Day 29	-3.0 Millimeters of Mercury (mmHg) Standard Deviation 6.63	0.5 Millimeters of Mercury (mmHg) Standard Deviation 9.19	-8.8 Millimeters of Mercury (mmHg) Standard Deviation 12.05	-6.3 Millimeters of Mercury (mmHg) Standard Deviation 13.76	-9.2 Millimeters of Mercury (mmHg) Standard Deviation 10.11
Change From Baseline in Diastolic Blood Pressure and Systolic Blood Pressure SBP, Day 57	7.8 Millimeters of Mercury (mmHg) Standard Deviation 7.93	-2.0 Millimeters of Mercury (mmHg) Standard Deviation 5.66	-3.4 Millimeters of Mercury (mmHg) Standard Deviation 13.98	3.7 Millimeters of Mercury (mmHg) Standard Deviation 11.33	-13.2 Millimeters of Mercury (mmHg) Standard Deviation 5.31
Change From Baseline in Diastolic Blood Pressure and Systolic Blood Pressure SBP, Day 85	4.3 Millimeters of Mercury (mmHg) Standard Deviation 8.58	6.5 Millimeters of Mercury (mmHg) Standard Deviation 13.44	-5.4 Millimeters of Mercury (mmHg) Standard Deviation 13.45	3.0 Millimeters of Mercury (mmHg) Standard Deviation 12.44	-13.7 Millimeters of Mercury (mmHg) Standard Deviation 7.99
Change From Baseline in Diastolic Blood Pressure and Systolic Blood Pressure SBP, Day 211	7.3 Millimeters of Mercury (mmHg) Standard Deviation 10.21	5.0 Millimeters of Mercury (mmHg) Standard Deviation 9.90	-3.6 Millimeters of Mercury (mmHg) Standard Deviation 15.21	10.0 Millimeters of Mercury (mmHg) Standard Deviation 13.49	-10.2 Millimeters of Mercury (mmHg) Standard Deviation 5.19
Change From Baseline in Diastolic Blood Pressure and Systolic Blood Pressure DBP, Day 29	-5.0 Millimeters of Mercury (mmHg) Standard Deviation 7.26	-0.5 Millimeters of Mercury (mmHg) Standard Deviation 9.19	-2.2 Millimeters of Mercury (mmHg) Standard Deviation 7.77	-4.0 Millimeters of Mercury (mmHg) Standard Deviation 8.65	-6.0 Millimeters of Mercury (mmHg) Standard Deviation 5.73
Change From Baseline in Diastolic Blood Pressure and Systolic Blood Pressure DBP, Day 211	4.3 Millimeters of Mercury (mmHg) Standard Deviation 6.95	8.0 Millimeters of Mercury (mmHg) Standard Deviation 8.49	0.8 Millimeters of Mercury (mmHg) Standard Deviation 9.88	6.8 Millimeters of Mercury (mmHg) Standard Deviation 6.37	-3.8 Millimeters of Mercury (mmHg) Standard Deviation 9.56
Change From Baseline in Diastolic Blood Pressure and Systolic Blood Pressure DBP, Day 57	0.0 Millimeters of Mercury (mmHg) Standard Deviation 9.38	3.0 Millimeters of Mercury (mmHg) Standard Deviation 4.24	-0.2 Millimeters of Mercury (mmHg) Standard Deviation 9.92	1.0 Millimeters of Mercury (mmHg) Standard Deviation 8.20	-3.0 Millimeters of Mercury (mmHg) Standard Deviation 11.06
Change From Baseline in Diastolic Blood Pressure and Systolic Blood Pressure DBP, Day 85	-1.8 Millimeters of Mercury (mmHg) Standard Deviation 6.08	4.5 Millimeters of Mercury (mmHg) Standard Deviation 14.85	0.1 Millimeters of Mercury (mmHg) Standard Deviation 12.43	2.2 Millimeters of Mercury (mmHg) Standard Deviation 6.71	-3.7 Millimeters of Mercury (mmHg) Standard Deviation 6.65

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Respiratory Rate was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=4 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Respiratory Rate Day 57	-0.8 Breaths/minute Standard Deviation 2.22	-2.5 Breaths/minute Standard Deviation 2.12	0.6 Breaths/minute Standard Deviation 0.67	-0.5 Breaths/minute Standard Deviation 1.87	0.2 Breaths/minute Standard Deviation 1.33
Change From Baseline in Respiratory Rate Day 85	-0.8 Breaths/minute Standard Deviation 2.22	-3.0 Breaths/minute Standard Deviation 1.41	0.5 Breaths/minute Standard Deviation 0.52	-0.3 Breaths/minute Standard Deviation 1.86	0.2 Breaths/minute Standard Deviation 0.41
Change From Baseline in Respiratory Rate Day 211	-1.0 Breaths/minute Standard Deviation 2.00	-3.0 Breaths/minute Standard Deviation 1.41	0.7 Breaths/minute Standard Deviation 0.78	-0.5 Breaths/minute Standard Deviation 1.97	0.0 Breaths/minute Standard Deviation 0.10
Change From Baseline in Respiratory Rate Day 29	-0.8 Breaths/minute Standard Deviation 2.22	-2.5 Breaths/minute Standard Deviation 2.12	0.7 Breaths/minute Standard Deviation 0.65	0.3 Breaths/minute Standard Deviation 1.03	0.3 Breaths/minute Standard Deviation 0.52

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Days 29, 57, 85, 211

Pulse Rate was measured at indicated timepoints. Baseline value is defined as last non-missing measurement prior to the first dose of study drug. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=4 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Pulse Rate Day 29	9.0 Beats/minute Standard Deviation 6.63	1.0 Beats/minute Standard Deviation 4.24	4.3 Beats/minute Standard Deviation 8.14	-4.7 Beats/minute Standard Deviation 13.63	1.5 Beats/minute Standard Deviation 5.32
Change From Baseline in Pulse Rate Day 57	16.0 Beats/minute Standard Deviation 6.06	8.0 Beats/minute Standard Deviation 4.24	8.2 Beats/minute Standard Deviation 14.33	-1.5 Beats/minute Standard Deviation 16.34	6.5 Beats/minute Standard Deviation 14.36
Change From Baseline in Pulse Rate Day 85	16.8 Beats/minute Standard Deviation 5.32	3.5 Beats/minute Standard Deviation 7.78	2.3 Beats/minute Standard Deviation 9.10	5.7 Beats/minute Standard Deviation 19.96	-1.7 Beats/minute Standard Deviation 7.15
Change From Baseline in Pulse Rate Day 211	16.3 Beats/minute Standard Deviation 8.42	13.0 Beats/minute Standard Deviation 2.83	2.9 Beats/minute Standard Deviation 8.70	-0.3 Beats/minute Standard Deviation 18.82	1.8 Beats/minute Standard Deviation 12.22

PRIMARY outcome

Timeframe: Up to Day 211

Population: Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Number of Participants With Abnormal Findings in Physical Examination	0 Participants	0 Participants	1 Participants	3 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to Day 211

Population: Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

A concomitant medication is defined as any medication initiated after the first dose of study, or initiated prior to the first dose of study drug and continued after the first dose of study drug.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Number of Participants Who Received Atleast One Concomitant Medication	5 Participants	2 Participants	8 Participants	4 Participants	5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose); Day1: 3 hours post-dose, 5 hours post-dose; Day 2; Day 22:pre-dose, 3 hours postdose, 5 hours post-dose; Days 23, 29 and 113

Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Triplicate 12-lead Electrocardiograms (ECGs) were recorded at indicated timepoints. At each time point, ECG machine automatically measured mean ventricular rate (VR). Baseline ECG was the average of the triplicate taken on Day 1 Pre-dose, if only 1 or 2 assessments were available, the single assessment or average of the 2 assessments was used. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Electrocardiogram Mean Ventricular Rate Mean VR, Day1, 3 hours Post-dose, n=6,12,6,5,2	8.2 Beats per minute Standard Deviation 4.60	10.0 Beats per minute Standard Deviation 2.83	5.6 Beats per minute Standard Deviation 8.85	4.3 Beats per minute Standard Deviation 5.05	4.5 Beats per minute Standard Deviation 4.93
Change From Baseline in Electrocardiogram Mean Ventricular Rate Mean VR, Day1, 5 hours Post-dose, n=6,12,6,5,2	12.6 Beats per minute Standard Deviation 6.88	8.0 Beats per minute Standard Deviation 9.90	2.0 Beats per minute Standard Deviation 7.93	1.8 Beats per minute Standard Deviation 6.52	4.7 Beats per minute Standard Deviation 6.22
Change From Baseline in Electrocardiogram Mean Ventricular Rate Mean VR, Day 2, n=6,12,6,5,2	22.8 Beats per minute Standard Deviation 9.15	5.5 Beats per minute Standard Deviation 7.78	10.1 Beats per minute Standard Deviation 12.93	-2.7 Beats per minute Standard Deviation 10.27	0.3 Beats per minute Standard Deviation 2.66
Change From Baseline in Electrocardiogram Mean Ventricular Rate Mean VR, Day 22, Pre-dose, n=5,12,6,4,2	0.8 Beats per minute Standard Deviation 4.86	-1.0 Beats per minute Standard Deviation 5.66	0.4 Beats per minute Standard Deviation 8.54	-3.6 Beats per minute Standard Deviation 5.46	1.0 Beats per minute Standard Deviation 6.54
Change From Baseline in Electrocardiogram Mean Ventricular Rate Mean VR, Day 22, 3 hours Post-dose, n=5,12,6,4,2	9.3 Beats per minute Standard Deviation 4.92	8.5 Beats per minute Standard Deviation 2.12	5.0 Beats per minute Standard Deviation 7.24	-1.4 Beats per minute Standard Deviation 7.37	3.7 Beats per minute Standard Deviation 5.47
Change From Baseline in Electrocardiogram Mean Ventricular Rate Mean VR, Day 22, 5 hours Post-dose, n=5,12,6,4,2	8.0 Beats per minute Standard Deviation 6.22	8.0 Beats per minute Standard Deviation 2.83	3.4 Beats per minute Standard Deviation 6.27	-1.8 Beats per minute Standard Deviation 10.47	-0.7 Beats per minute Standard Deviation 5.82
Change From Baseline in Electrocardiogram Mean Ventricular Rate Mean VR, Day 23, n=5,12,6,4,2	10.3 Beats per minute Standard Deviation 4.92	0.0 Beats per minute Standard Deviation 4.24	6.3 Beats per minute Standard Deviation 3.65	-2.4 Beats per minute Standard Deviation 8.26	1.3 Beats per minute Standard Deviation 4.76
Change From Baseline in Electrocardiogram Mean Ventricular Rate Mean VR, Day 29, n=6,12,6,4,2	7.3 Beats per minute Standard Deviation 6.13	3.5 Beats per minute Standard Deviation 7.78	2.8 Beats per minute Standard Deviation 7.63	-1.3 Beats per minute Standard Deviation 11.60	0.2 Beats per minute Standard Deviation 4.45
Change From Baseline in Electrocardiogram Mean Ventricular Rate Mean VR, Day 113, n=6,12,6,4,2	8.3 Beats per minute Standard Deviation 2.06	8.0 Beats per minute Standard Deviation 9.90	2.5 Beats per minute Standard Deviation 10.60	-5.2 Beats per minute Standard Deviation 9.75	-2.3 Beats per minute Standard Deviation 6.06

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose); Day1: 3 hours post-dose, 5 hours post-dose; Day 2; Day 22:pre-dose, 3 hours postdose, 5 hours post-dose; Days 23, 29 and 113

Triplicate 12-lead Electrocardiograms (ECGs) were recorded at indicated timepoints. At each time point, ECG machine automatically measured QRS duration, uncorrected QT interval, QT corrected interval-Fredericia \[QTcF\] interval and QTc corrected by Bazett's formula (QTcB). Baseline ECG was the average of the triplicate taken on Day 1 Pre-dose, if only 1 or 2 assessments were available, the single assessment or average of the 2 assessments was used. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula PR, Day 1,3 hours Post-dose, n=6,11,6,5,2	0.8 Milliseconds Standard Deviation 8.41	7.0 Milliseconds Standard Deviation 1.41	1.8 Milliseconds Standard Deviation 9.99	-1.2 Milliseconds Standard Deviation 8.42	3.5 Milliseconds Standard Deviation 30.84
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula PR, Day 1, 5 hours Post-dose, n=6,11,6,5,2	1.4 Milliseconds Standard Deviation 8.38	-3.0 Milliseconds Standard Deviation 0.00	1.3 Milliseconds Standard Deviation 8.37	-1.7 Milliseconds Standard Deviation 8.64	10.8 Milliseconds Standard Deviation 33.52
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula PR, Day 2, n=6,12,6,5,2	-2.4 Milliseconds Standard Deviation 8.79	5.5 Milliseconds Standard Deviation 2.12	0.7 Milliseconds Standard Deviation 15.78	1.0 Milliseconds Standard Deviation 4.65	12.2 Milliseconds Standard Deviation 21.45
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula PR, Day 22, Pre-dose, n=5,12,6,4,2	-2.8 Milliseconds Standard Deviation 10.87	8.0 Milliseconds Standard Deviation 7.07	-2.4 Milliseconds Standard Deviation 11.70	7.0 Milliseconds Standard Deviation 14.27	11.0 Milliseconds Standard Deviation 19.84
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula PR, Day 22, 3 hours Post-dose, n=5,12,6,4,2	-6.5 Milliseconds Standard Deviation 11.79	7.5 Milliseconds Standard Deviation 6.36	0.3 Milliseconds Standard Deviation 14.51	2.0 Milliseconds Standard Deviation 7.21	9.2 Milliseconds Standard Deviation 21.51
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula PR, Day 22, 5 hours Post-dose, n=5,11,6,4,2	-7.0 Milliseconds Standard Deviation 9.42	5.5 Milliseconds Standard Deviation 4.95	-2.3 Milliseconds Standard Deviation 14.18	-0.2 Milliseconds Standard Deviation 10.03	9.0 Milliseconds Standard Deviation 22.82
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula PR, Day 23, n=5,11,6,4,2	-1.0 Milliseconds Standard Deviation 7.79	4.5 Milliseconds Standard Deviation 3.54	-1.6 Milliseconds Standard Deviation 11.09	9.4 Milliseconds Standard Deviation 12.03	11.2 Milliseconds Standard Deviation 21.77
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula PR, Day 29, n=6,12,6,4,2	-1.8 Milliseconds Standard Deviation 4.72	10.0 Milliseconds Standard Deviation 4.24	-1.7 Milliseconds Standard Deviation 11.67	4.8 Milliseconds Standard Deviation 7.28	7.3 Milliseconds Standard Deviation 17.64
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula PR, Day 113, n=6,12,6,4,2	-2.0 Milliseconds Standard Deviation 8.83	6.0 Milliseconds Standard Deviation 7.07	-1.6 Milliseconds Standard Deviation 14.48	7.7 Milliseconds Standard Deviation 8.82	14.3 Milliseconds Standard Deviation 21.81
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QRS duration, Day1, 3 hours Post-dose,n=6,12,6,5,2	1.0 Milliseconds Standard Deviation 2.00	-1.5 Milliseconds Standard Deviation 3.54	-0.2 Milliseconds Standard Deviation 5.08	0.8 Milliseconds Standard Deviation 3.97	2.2 Milliseconds Standard Deviation 4.31
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QRS duration, Day1, 5 hours Post-dose,n=6,12,6,5,2	0.4 Milliseconds Standard Deviation 1.95	-3.0 Milliseconds Standard Deviation 4.24	-1.7 Milliseconds Standard Deviation 4.38	-0.8 Milliseconds Standard Deviation 2.04	6.0 Milliseconds Standard Deviation 4.98
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QRS duration, Day 2, n=6,12,6,5,2	-2.2 Milliseconds Standard Deviation 4.87	-0.5 Milliseconds Standard Deviation 0.71	0.8 Milliseconds Standard Deviation 3.98	0.5 Milliseconds Standard Deviation 3.94	3.7 Milliseconds Standard Deviation 8.07
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QRS duration, Day 22, Pre-dose, n=5,12,6,4,2	-0.8 Milliseconds Standard Deviation 4.79	-4.0 Milliseconds Standard Deviation 2.83	-3.6 Milliseconds Standard Deviation 5.07	0.2 Milliseconds Standard Deviation 3.11	4.2 Milliseconds Standard Deviation 3.19
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QRS duration, Day 22, 3 hours Post-dose, n=5,12,6,4,2	2.5 Milliseconds Standard Deviation 1.91	-1.0 Milliseconds Standard Deviation 0.00	-1.2 Milliseconds Standard Deviation 4.11	1.6 Milliseconds Standard Deviation 3.51	5.0 Milliseconds Standard Deviation 6.99
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QRS duration, Day 22, 5 hours Post-dose, n=5,12,6,4,2	-0.3 Milliseconds Standard Deviation 5.12	-2.0 Milliseconds Standard Deviation 1.41	-1.0 Milliseconds Standard Deviation 3.86	1.0 Milliseconds Standard Deviation 5.15	6.3 Milliseconds Standard Deviation 5.28
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QRS duration, Day 23, n=5,12,6,4,2	-0.5 Milliseconds Standard Deviation 4.12	1.5 Milliseconds Standard Deviation 3.54	0.9 Milliseconds Standard Deviation 3.09	-0.4 Milliseconds Standard Deviation 5.37	0.3 Milliseconds Standard Deviation 7.00
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QRS duration, Day 29, n=6,12,6,4,2	3.0 Milliseconds Standard Deviation 6.98	0.5 Milliseconds Standard Deviation 0.71	0.7 Milliseconds Standard Deviation 4.91	0.3 Milliseconds Standard Deviation 4.18	5.5 Milliseconds Standard Deviation 7.50
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QRS duration, Day 113, n=6,12,6,4,2	-2.8 Milliseconds Standard Deviation 5.19	1.0 Milliseconds Standard Deviation 1.41	0.0 Milliseconds Standard Deviation 4.90	0.3 Milliseconds Standard Deviation 5.72	4.7 Milliseconds Standard Deviation 8.09
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QT, Day 1, 3 hours Post-dose, n=6,12,6,5,2	-23.8 Milliseconds Standard Deviation 9.55	-20.5 Milliseconds Standard Deviation 0.71	-12.4 Milliseconds Standard Deviation 17.30	-11.8 Milliseconds Standard Deviation 14.85	-5.7 Milliseconds Standard Deviation 8.21
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QT, Day 1, 5 hours Post-dose, n=6,12,6,5,2	-37.6 Milliseconds Standard Deviation 19.89	-21.0 Milliseconds Standard Deviation 11.31	-10.3 Milliseconds Standard Deviation 18.25	-11.3 Milliseconds Standard Deviation 19.41	-7.3 Milliseconds Standard Deviation 12.80
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QT, Day 2, n=6,12,6,5,2	-62.8 Milliseconds Standard Deviation 19.38	19.5 Milliseconds Standard Deviation 19.09	-25.5 Milliseconds Standard Deviation 29.57	-0.3 Milliseconds Standard Deviation 29.34	0.3 Milliseconds Standard Deviation 6.41
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QT, Day 22, Pre-dose, n=5,12,6,4,2	-1.0 Milliseconds Standard Deviation 12.68	3.0 Milliseconds Standard Deviation 11.31	1.9 Milliseconds Standard Deviation 17.05	15.2 Milliseconds Standard Deviation 12.91	2.0 Milliseconds Standard Deviation 19.65
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QT, Day 22, 3 hours Post-dose, n=5,12,6,4,2	-27.3 Milliseconds Standard Deviation 22.47	-16.0 Milliseconds Standard Deviation 12.73	-8.7 Milliseconds Standard Deviation 21.05	11.2 Milliseconds Standard Deviation 30.60	-3.0 Milliseconds Standard Deviation 17.31
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QT, Day 22, 5 hours Post-dose, n=5,12,6,4,2	-25.3 Milliseconds Standard Deviation 23.73	-17.5 Milliseconds Standard Deviation 9.19	-8.0 Milliseconds Standard Deviation 18.68	5.8 Milliseconds Standard Deviation 29.71	2.5 Milliseconds Standard Deviation 16.31
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QT, Day 23, n=5,12,6,4,2	-30.5 Milliseconds Standard Deviation 18.81	-8.5 Milliseconds Standard Deviation 6.36	-13.9 Milliseconds Standard Deviation 13.81	8.0 Milliseconds Standard Deviation 23.63	-5.2 Milliseconds Standard Deviation 16.74
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QT, Day 29, n=6,12,6,4,2	-23.0 Milliseconds Standard Deviation 16.02	-4.0 Milliseconds Standard Deviation 31.11	-5.4 Milliseconds Standard Deviation 20.97	9.0 Milliseconds Standard Deviation 31.92	2.5 Milliseconds Standard Deviation 15.45
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QT, Day 113, n=6,12,6,4,2	-28.3 Milliseconds Standard Deviation 13.33	-20.0 Milliseconds Standard Deviation 22.63	-15.4 Milliseconds Standard Deviation 49.82	13.7 Milliseconds Standard Deviation 30.59	4.2 Milliseconds Standard Deviation 17.95
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcB, Day 1,3 hours Post-dose, n=1,3,2,0,0	—	—	3.3 Milliseconds Standard Deviation 3.06	5.0 Milliseconds Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	3.0 Milliseconds Standard Deviation 1.41
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcB, Day 1, 5 hours Post-dose, n=1,3,2,0,0	—	—	-1.3 Milliseconds Standard Deviation 11.02	-9.0 Milliseconds Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	4.5 Milliseconds Standard Deviation 0.71
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcB, Day 2, n=1,3,2,0,0	—	—	4.3 Milliseconds Standard Deviation 7.57	-3.0 Milliseconds Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	2.5 Milliseconds Standard Deviation 0.71
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcB, Day 22, Pre-dose, n=1,3,2,0,0	—	—	7.3 Milliseconds Standard Deviation 6.43	27.0 Milliseconds Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	-0.5 Milliseconds Standard Deviation 7.78
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcB, Day 22, 3 hours Post-dose, n=1,3,2,0,0	—	—	18.7 Milliseconds Standard Deviation 16.77	16.0 Milliseconds Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	-2.0 Milliseconds Standard Deviation 2.83
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcB, Day 22, 5 hours Post-dose, n=1,3,2,0,0	—	—	3.7 Milliseconds Standard Deviation 2.31	11.0 Milliseconds Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	-14.5 Milliseconds Standard Deviation 6.36
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcB, Day 23, n=1,3,2,0,0	—	—	7.3 Milliseconds Standard Deviation 8.62	14.0 Milliseconds Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	-3.5 Milliseconds Standard Deviation 7.78
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcB, Day 29, n=1,4,2,0,0	—	—	3.0 Milliseconds Standard Deviation 8.98	21.0 Milliseconds Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	6.5 Milliseconds Standard Deviation 6.36
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcF, Day 23, n=4,8,4,4,2	-5.0 Milliseconds Standard Deviation 9.20	-10.0 Milliseconds Standard Deviation 0.00	-3.3 Milliseconds Standard Deviation 9.82	-0.8 Milliseconds Standard Deviation 8.38	-0.5 Milliseconds Standard Deviation 7.05
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcB, Day 113, n=1,5,3,0,0	—	—	-1.8 Milliseconds Standard Deviation 3.27	5.0 Milliseconds Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	-13.0 Milliseconds Standard Deviation 8.54
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcF, Day 1,3 hours Post-dose, n=5,9,4,5,2	-3.8 Milliseconds Standard Deviation 13.88	-4.5 Milliseconds Standard Deviation 4.95	-1.9 Milliseconds Standard Deviation 8.16	-6.0 Milliseconds Standard Deviation 6.28	3.5 Milliseconds Standard Deviation 7.05
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcF, Day 1,5 hours Post-dose, n=5,9,4,5,2	-9.0 Milliseconds Standard Deviation 13.84	-7.5 Milliseconds Standard Deviation 6.36	-8.9 Milliseconds Standard Deviation 8.49	-9.6 Milliseconds Standard Deviation 10.67	1.3 Milliseconds Standard Deviation 5.32
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcF, Day 2, n=4,8,4,5,2	-44.6 Milliseconds Standard Deviation 65.50	-11.0 Milliseconds Standard Deviation 5.66	-12.5 Milliseconds Standard Deviation 9.01	-8.6 Milliseconds Standard Deviation 13.50	-1.0 Milliseconds Standard Deviation 4.69
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcF, Day 22, Pre-dose, n=5,9,4,4,2	1.3 Milliseconds Standard Deviation 3.77	-1.5 Milliseconds Standard Deviation 2.12	0.7 Milliseconds Standard Deviation 12.19	-1.0 Milliseconds Standard Deviation 2.94	8.8 Milliseconds Standard Deviation 8.88
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcF, Day 22, 3 hours Post-dose, n=4,9,4,4,2	-4.5 Milliseconds Standard Deviation 13.48	-1.5 Milliseconds Standard Deviation 10.61	-1.0 Milliseconds Standard Deviation 11.10	0.8 Milliseconds Standard Deviation 10.08	9.5 Milliseconds Standard Deviation 10.47
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcF, Day 22, 5 hours Post-dose, n=4,9,4,5,2	-5.8 Milliseconds Standard Deviation 12.55	-4.5 Milliseconds Standard Deviation 4.95	-3.6 Milliseconds Standard Deviation 12.97	-5.0 Milliseconds Standard Deviation 7.66	5.8 Milliseconds Standard Deviation 9.95
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcF, Day 29, n=5,8,4,4,2	-5.5 Milliseconds Standard Deviation 10.08	-4.5 Milliseconds Standard Deviation 10.61	-0.1 Milliseconds Standard Deviation 9.60	4.0 Milliseconds Standard Deviation 22.55	3.0 Milliseconds Standard Deviation 8.98
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval and QTc Corrected by Bazett's Formula QTcF, Day 113, n=5,6,3,4,2	-6.5 Milliseconds Standard Deviation 10.75	-7.0 Milliseconds Standard Deviation 5.66	-1.0 Milliseconds Standard Deviation 14.09	-1.08 Milliseconds Standard Deviation 20.24	4.0 Milliseconds Standard Deviation 12.29

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 29

Population: Full Analysis Set Population comprised of practically-feasible Intent-to-treat population, including subset of the Safety Set with a Baseline and at least 1 post-Baseline plasma HBV DNA concentration. Only those participants with data available at the specified data points were analyzed. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision,hence Cohort 2 and Cohort 3 have been combined.

Blood samples were collected from participants to assess HBV DNA viral load. Baseline is the last non-missing measurement prior to the first dose of study drug. The concentrations were logarithmic transformed with base 10 in this analysis. Change from Baseline is defined as post-dose visit value minus Baseline value. The last observation carried forward (LOCF) method was used to impute missing values at Day 29 in this analysis.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Day 29	0.075 Log10 (International Units/milliliter) Standard Deviation 0.1667	0.000 Log10 (International Units/milliliter) Standard Deviation 0.0000	-1.655 Log10 (International Units/milliliter) Standard Deviation 1.4791	-0.384 Log10 (International Units/milliliter) Standard Deviation 0.4199	-0.001 Log10 (International Units/milliliter) Standard Deviation 0.4710

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Week 31

Population: Full Analysis Set Population. Only those participants with data available at the specified data points were analyzed. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=3 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=1 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=5 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=5 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Week 31	0.000 Log10 (International Units/milliliter) Standard Deviation 0.0000	0.000 Log10 (International Units/milliliter) Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.	-4.770 Log10 (International Units/milliliter) Standard Deviation 1.2823	-4.754 Log10 (International Units/milliliter) Standard Deviation 0.8344	-3.547 Log10 (International Units/milliliter) Standard Deviation 1.2798

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 29

Blood samples were collected from participants to assess HBsAg level. Baseline is the last non-missing measurement prior to the first dose of study drug. The concentrations were logarithmic transformed with base 10 in this analysis. Change from Baseline is defined as post-dose visit value minus Baseline value. The LOCF method was used to impute missing values at Day 29 in this analysis.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in HBV Surface Antigen (HBsAg) Level in Serum at Day 29	-1.986 Log10 (International Units/milliliter) Standard Deviation 1.7986	-0.008 Log10 (International Units/milliliter) Standard Deviation 0.0390	-1.556 Log10 (International Units/milliliter) Standard Deviation 1.3787	-0.504 Log10 (International Units/milliliter) Standard Deviation 0.5656	0.000 Log10 (International Units/milliliter) Standard Deviation 0.1116

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Week 31

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=4 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in HBsAg Level in Serum at Week 31	-1.519 Log10 (International Units/milliliter) Standard Deviation 1.4821	-0.043 Log10 (International Units/milliliter) Standard Deviation 0.0178	-0.547 Log10 (International Units/milliliter) Standard Deviation 0.6109	-0.523 Log10 (International Units/milliliter) Standard Deviation 0.9299	0.059 Log10 (International Units/milliliter) Standard Deviation 0.3859

SECONDARY outcome

Timeframe: At Day 29 and Week 31

Population: Full Analysis Set Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Blood samples were collected to evaluate the percentage of participants with HBsAg loss at Day 29 and Week 31. A 'Loss' of HBsAg means antigen is negative. HBsAg Loss percentage is defined as number of participants with HBsAg loss divided by total number of participants assessed multiplied by 100. Baseline is the last non-missing measurement prior to the first dose of study drug.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg n=5 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 Participants Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Percentage of Participants Who Achieved HBsAg Loss at Day 29 and Week 31 Day 29	20.0 Percentage of Participants	0 Percentage of Participants	16.7 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants Who Achieved HBsAg Loss at Day 29 and Week 31 Week 31	0 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre dose) and at Day 29 and Week 31

Population: Full Analysis Set Population. Only those participants with data available at the specified data points were analyzed. None of the participants were HBeAg positive at Baseline in Cohort 4, hence no data to report (N=0) for Cohort 4 arms. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Blood samples were collected to evaluate the percentage of participants with HBeAg loss at Day 29 and Week 31. A 'Loss' of HBeAg means antigen is negative. HBeAg Loss percentage is defined as number of participants with HBeAg loss divided by number of participants with positive HBeAg at Baseline multiplied by 100. Baseline is the last non-missing measurement prior to the first dose of study drug. Participants was considered HBeAg positive at Baseline if the Baseline value\> 0.09 U/mL.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=5 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=2 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Percentage of Participants Who Achieved HBV e Antigen (HBeAg) Loss at Day 29 and Week 31 Who Were HBeAg Positive at Baseline Day 29	—	—	0 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants Who Achieved HBV e Antigen (HBeAg) Loss at Day 29 and Week 31 Who Were HBeAg Positive at Baseline Week 31	—	—	0 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre dose) and at Day 29

Blood samples were collected from participants to assess HBeAg level. Baseline is the last non-missing measurement prior to the first dose of study drug. The concentrations were logarithmic transformed with base 10 in this analysis. Change from Baseline is defined as post-dose visit value minus Baseline value. Participant was considered HBeAg positive at Baseline if the Baseline value\> 0.09 International Units/milliliter (IU/mL).

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=5 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=2 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Serum HBeAg Concentration at Day 29 in Participants Who Were HBeAg Positive at Baseline	—	—	-0.052 Log10 (IU/mL) Standard Deviation 0.6741	-0.004 Log10 (IU/mL) Standard Deviation 0.3967	0.133 Log10 (IU/mL) Standard Deviation 0.2884

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre dose) and Week 31

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=5 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=2 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Change From Baseline in Serum HBeAg Concentration at Week 31 in Participants Who Were HBeAg Positive at Baseline	—	—	-0.195 Log10 IU/mL Standard Deviation 0.5047	-0.577 Log10 IU/mL Standard Deviation 1.3711	0.131 Log10 IU/mL Standard Deviation 0.7477

SECONDARY outcome

Timeframe: Day 1:pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hours post-dose, Days 2 and 23: 24 hours post-dose, Day 4: 72 hours post-dose, Days 8 and 15: pre-dose, Day 22: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hours post-dose, and Days 29, 36, 57, 85, 113, and 211

Population: Pharmacokinetic Population consisted of participants who were randomized, received at least 1 dose of study drug, and had at least 1 valid pharmacokinetic metric. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Plasma samples were collected from participants with chronic HBV infection at indicated time points for pharmacokinetic analysis of GSK3228836.

Outcome measures

Outcome measures
Measure	Cohort 4 GSK3228836 300 mg Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 Participants Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 1 GSK3228836 150 mg n=6 Participants Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=5 Participants Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 1, pre-dose, n=6,12,5	—	—	0.00 Nanogram per milliliter Standard Deviation 0.000	0.00 Nanogram per milliliter Standard Deviation 0.000	0.00 Nanogram per milliliter Standard Deviation 0.000
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 1, 0.5 hour post-dose, n=6,12,5	—	—	2145.58 Nanogram per milliliter Standard Deviation 1295.533	1187.00 Nanogram per milliliter Standard Deviation 1052.256	1630.00 Nanogram per milliliter Standard Deviation 539.583
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 1, 1 hour post-dose, n=6,11,5	—	—	4950.91 Nanogram per milliliter Standard Deviation 2025.302	1909.33 Nanogram per milliliter Standard Deviation 1287.383	4074.00 Nanogram per milliliter Standard Deviation 1314.565
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 1, 1.5 hours post-dose, n=6,12,5	—	—	6536.67 Nanogram per milliliter Standard Deviation 2710.704	2440.00 Nanogram per milliliter Standard Deviation 1515.823	6100.00 Nanogram per milliliter Standard Deviation 1816.631
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 1, 2 hours post-dose, n=6,12,5	—	—	8387.50 Nanogram per milliliter Standard Deviation 3287.981	2976.67 Nanogram per milliliter Standard Deviation 1444.793	7556.00 Nanogram per milliliter Standard Deviation 2672.579
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 1, 5 hours post-dose, n=6,12,5	—	—	9813.33 Nanogram per milliliter Standard Deviation 3524.376	3210.00 Nanogram per milliliter Standard Deviation 1156.962	9122.00 Nanogram per milliliter Standard Deviation 2616.662
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 1, 6 hours post-dose, n=6,12,5	—	—	9345.00 Nanogram per milliliter Standard Deviation 3258.863	2933.33 Nanogram per milliliter Standard Deviation 986.097	8580.00 Nanogram per milliliter Standard Deviation 2203.418
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 8, pre-dose, n=6,12,4	—	—	22.07 Nanogram per milliliter Standard Deviation 7.715	7.69 Nanogram per milliliter Standard Deviation 4.540	21.80 Nanogram per milliliter Standard Deviation 6.458
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 15, pre-dose, n=6,12,4	—	—	30.29 Nanogram per milliliter Standard Deviation 12.598	10.90 Nanogram per milliliter Standard Deviation 4.989	33.33 Nanogram per milliliter Standard Deviation 11.536
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 22, 1 hour post-dose, n=5,12,4	—	—	4815.83 Nanogram per milliliter Standard Deviation 1835.595	2133.00 Nanogram per milliliter Standard Deviation 1616.738	3477.50 Nanogram per milliliter Standard Deviation 2009.766
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 22, 1.5 hours post-dose, n=5,12,4	—	—	7094.17 Nanogram per milliliter Standard Deviation 2862.178	2874.00 Nanogram per milliliter Standard Deviation 1872.173	5235.00 Nanogram per milliliter Standard Deviation 3036.341
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 23, 24 hours post-dose, n=5,12,4	—	—	387.88 Nanogram per milliliter Standard Deviation 209.944	152.90 Nanogram per milliliter Standard Deviation 148.879	524.00 Nanogram per milliliter Standard Deviation 372.305
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 29, n=5,12,4	—	—	23.42 Nanogram per milliliter Standard Deviation 9.358	8.88 Nanogram per milliliter Standard Deviation 1.680	21.50 Nanogram per milliliter Standard Deviation 4.883
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 36, n=5,12,4	—	—	12.58 Nanogram per milliliter Standard Deviation 6.332	5.32 Nanogram per milliliter Standard Deviation 1.098	8.96 Nanogram per milliliter Standard Deviation 3.246
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 211, n=5,12,4	—	—	1.04 Nanogram per milliliter Standard Deviation 2.438	0.38 Nanogram per milliliter Standard Deviation 0.845	0.37 Nanogram per milliliter Standard Deviation 0.730
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 1, 3 hours post-dose, n=6,12,5	—	—	9905.00 Nanogram per milliliter Standard Deviation 3494.308	3360.00 Nanogram per milliliter Standard Deviation 1614.955	8916.00 Nanogram per milliliter Standard Deviation 2541.324
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 1, 4 hours post-dose, n=6,12,5	—	—	9658.33 Nanogram per milliliter Standard Deviation 3612.189	3340.00 Nanogram per milliliter Standard Deviation 1223.781	9632.00 Nanogram per milliliter Standard Deviation 2115.401
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 2, 24 hours post dose, n=6,12,5	—	—	336.88 Nanogram per milliliter Standard Deviation 301.302	112.22 Nanogram per milliliter Standard Deviation 79.406	356.00 Nanogram per milliliter Standard Deviation 140.490
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 4 , 72 hours post-dose, n=6,12,5	—	—	12.92 Nanogram per milliliter Standard Deviation 3.975	6.77 Nanogram per milliliter Standard Deviation 2.759	15.24 Nanogram per milliliter Standard Deviation 3.138
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 22, pre-dose, n=5,12,4	—	—	22.85 Nanogram per milliliter Standard Deviation 9.848	9.38 Nanogram per milliliter Standard Deviation 2.279	25.43 Nanogram per milliliter Standard Deviation 7.630
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 22 0.5 hour pre-dose, n=5,12,4	—	—	2073.58 Nanogram per milliliter Standard Deviation 883.806	1315.40 Nanogram per milliliter Standard Deviation 1064.380	1447.75 Nanogram per milliliter Standard Deviation 850.592
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 22, 2 hours post-dose, n=5,12,4	—	—	8351.67 Nanogram per milliliter Standard Deviation 3274.596	3466.00 Nanogram per milliliter Standard Deviation 2033.158	6765.00 Nanogram per milliliter Standard Deviation 3805.422
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 22, 3 hours post-dose, n=5,12,4	—	—	9137.50 Nanogram per milliliter Standard Deviation 3303.139	4070.00 Nanogram per milliliter Standard Deviation 2146.742	8325.00 Nanogram per milliliter Standard Deviation 5007.950
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 22, 4 hours post-dose, n=5,12,4	—	—	8650.00 Nanogram per milliliter Standard Deviation 2913.339	3760.00 Nanogram per milliliter Standard Deviation 1572.260	8690.00 Nanogram per milliliter Standard Deviation 4808.791
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 22, 5 hours post-dose, n=5,12,4	—	—	8072.50 Nanogram per milliliter Standard Deviation 2748.322	3566.00 Nanogram per milliliter Standard Deviation 1229.504	8027.50 Nanogram per milliliter Standard Deviation 4274.166
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 22, 6 hours post-dose, n=5,12,4	—	—	7769.17 Nanogram per milliliter Standard Deviation 2295.697	2990.00 Nanogram per milliliter Standard Deviation 817.099	7447.50 Nanogram per milliliter Standard Deviation 3817.376
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 57, n=5,12,4	—	—	3.80 Nanogram per milliliter Standard Deviation 1.294	1.91 Nanogram per milliliter Standard Deviation 0.405	1.90 Nanogram per milliliter Standard Deviation 0.752
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 85, n=5,12,4	—	—	1.32 Nanogram per milliliter Standard Deviation 0.872	0.00 Nanogram per milliliter Standard Deviation 0.00	0.31 Nanogram per milliliter Standard Deviation 0.625
Plasma Concentrations of GSK3228836 in Participants With Chronic HBV Infection Day 133, n=5,12,4	—	—	0.59 Nanogram per milliliter Standard Deviation 0.619	0.91 Nanogram per milliliter Standard Deviation 1.273	0.00 Nanogram per milliliter Standard Deviation 0.00

Adverse Events

Cohort 1 GSK3228836 150 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort 2 and Cohort 3 GSK3228836 300 mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Cohorts 1-3 Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 4 GSK3228836 300 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort 4 Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 GSK3228836 150 mg n=6 participants at risk Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 participants at risk Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 participants at risk Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 GSK3228836 300 mg n=5 participants at risk Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 participants at risk Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.
Investigations Alanine aminotransferase increased	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Other adverse events

Other adverse events
Measure	Cohort 1 GSK3228836 150 mg n=6 participants at risk Treatment-naive participants were subcutaneously administered GSK3228836 150 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 2 and Cohort 3 GSK3228836 300 mg n=12 participants at risk Treatment-naive participants were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohorts 1-3 Placebo n=6 participants at risk Treatment-naive participants were subcutaneously administered placebo on Days 1, 4, 8, 11, 15, and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 GSK3228836 300 mg n=5 participants at risk Participants on stable nucleos(t)ide treatment were subcutaneously administered GSK3228836 300 mg on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.	Cohort 4 Placebo n=2 participants at risk Participants on stable nucleos(t)ide treatment were subcutaneously administered placebo on Days 1, 4, 8, 11, 15 and 22 by trained study center personnel in abdomen, upper arm or thigh.
General disorders Chest discomfort	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
General disorders Injection site bruising	16.7% 1/6 • Number of events 2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/12 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	20.0% 1/5 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
General disorders Injection site erythema	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	25.0% 3/12 • Number of events 9 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	20.0% 1/5 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
General disorders Injection site pain	16.7% 1/6 • Number of events 2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
General disorders Injection site pruritus	33.3% 2/6 • Number of events 5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
General disorders Injection site rash	16.7% 1/6 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/12 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
General disorders Injection site swelling	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	16.7% 2/12 • Number of events 3 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	20.0% 1/5 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
General disorders Pyrexia	16.7% 1/6 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	25.0% 3/12 • Number of events 5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	16.7% 1/6 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	20.0% 1/5 • Number of events 2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Gastrointestinal disorders Abdominal discomfort	16.7% 1/6 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/12 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Gastrointestinal disorders Mouth swelling	16.7% 1/6 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/12 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Gastrointestinal disorders Nausea	16.7% 1/6 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	16.7% 2/12 • Number of events 2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	16.7% 1/6 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Blood and lymphatic system disorders Anaemia	16.7% 1/6 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Infections and infestations Hand-foot-and-mouth disease	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Infections and infestations Influenza	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Investigations Alanine aminotransferase increased	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Investigations C-reactive protein increased	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	16.7% 2/12 • Number of events 2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Nervous system disorders Headache	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	16.7% 2/12 • Number of events 2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	16.7% 1/6 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Skin and subcutaneous tissue disorders Post inflammatory pigmentation change	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Injury, poisoning and procedural complications Contusion	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	8.3% 1/12 • Number of events 1 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/6 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/5 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.	0.00% 0/2 • Non-serious (>=5%) and serious adverse events were collected up to Day 211 Non-serious and serious adverse events were collected in the Safety Population. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial
Publication restrictions are in place

Restriction type: OTHER