Trial Outcomes & Findings for Proof of Mechanism Study of GSK2330811 in Diffuse Cutaneous Systemic Sclerosis (NCT NCT03041025)

Last Updated: 2021-05-24

Results Overview

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician. SAEs were collected up to Day 197, but the protocol also allowed investigators to report SAEs occurring after participants had completed the study. This outcome measure includes two SAEs reported after participants had completed the study, occurring on Day 306 and Day 603 following first dose. Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Up to Day 197, but protocol allowed for additional events to be collected; up to Day 603 post first dose

Results posted on

2021-05-24

Participant Flow

This was a randomized, double-blind (sponsor open), proof of mechanism study of GSK2330811 in participants with diffuse cutaneous systemic sclerosis. This study was conducted in Canada, Netherlands, United Kingdom and United States.

A total of 35 participants were enrolled in this study.

Participant milestones

Participant milestones
Measure	Placebo Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Overall Study STARTED	8	3	24
Overall Study COMPLETED	7	3	22
Overall Study NOT COMPLETED	1	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Overall Study Adverse Event	0	1
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Proof of Mechanism Study of GSK2330811 in Diffuse Cutaneous Systemic Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=24 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).	Total n=35 Participants Total of all reporting groups
Age, Continuous	50.8 Years STANDARD_DEVIATION 15.42 • n=5 Participants	66.7 Years STANDARD_DEVIATION 4.73 • n=7 Participants	52.6 Years STANDARD_DEVIATION 12.59 • n=5 Participants	53.4 Years STANDARD_DEVIATION 13.24 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	1 Participants n=7 Participants	19 Participants n=5 Participants	26 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	7 Participants n=5 Participants	3 Participants n=7 Participants	20 Participants n=5 Participants	30 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to Day 197, but protocol allowed for additional events to be collected; up to Day 603 post first dose

Population: Safety Population.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=24 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) Non-SAEs	8 Participants	3 Participants	24 Participants
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) SAEs	1 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC count. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze the hematology parameters: hemoglobin and MCHC. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 15: MCHC, n=8,3,23	0.9 Grams per liter Standard Deviation 8.53	-5.0 Grams per liter Standard Deviation 3.00	2.4 Grams per liter Standard Deviation 7.83
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 29: MCHC, n=8,3,23	-3.6 Grams per liter Standard Deviation 6.39	2.0 Grams per liter Standard Deviation 13.11	2.0 Grams per liter Standard Deviation 8.30
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 43: MCHC, n=8,3,22	-1.3 Grams per liter Standard Deviation 9.27	1.0 Grams per liter Standard Deviation 7.55	2.5 Grams per liter Standard Deviation 4.86
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 57: MCHC, n=6,3,22	-1.2 Grams per liter Standard Deviation 10.11	3.7 Grams per liter Standard Deviation 4.93	2.8 Grams per liter Standard Deviation 8.42
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 71: MCHC, n=8,3,20	2.3 Grams per liter Standard Deviation 12.87	2.7 Grams per liter Standard Deviation 6.81	0.5 Grams per liter Standard Deviation 8.62
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 85: MCHC, n=7,3,22	3.3 Grams per liter Standard Deviation 10.53	-1.7 Grams per liter Standard Deviation 9.50	2.8 Grams per liter Standard Deviation 6.68
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 113: MCHC, n=7,3,20	-0.4 Grams per liter Standard Deviation 7.18	5.0 Grams per liter Standard Deviation 8.19	-3.3 Grams per liter Standard Deviation 8.16
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 155: MCHC, n=7,3,17	-1.4 Grams per liter Standard Deviation 5.26	3.7 Grams per liter Standard Deviation 4.16	-4.2 Grams per liter Standard Deviation 9.35
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 197: MCHC, n=7,3,15	-0.4 Grams per liter Standard Deviation 8.58	-0.3 Grams per liter Standard Deviation 7.02	-3.5 Grams per liter Standard Deviation 8.18
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 15: Hemoglobin, n=8,3,23	-2.8 Grams per liter Standard Deviation 8.89	2.0 Grams per liter Standard Deviation 7.00	-0.2 Grams per liter Standard Deviation 5.31
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 29: Hemoglobin, n=8,3,23	-2.5 Grams per liter Standard Deviation 6.55	-0.7 Grams per liter Standard Deviation 11.06	-3.7 Grams per liter Standard Deviation 7.45
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 43: Hemoglobin, n=8,3,23	-2.5 Grams per liter Standard Deviation 6.39	-1.7 Grams per liter Standard Deviation 8.50	-7.7 Grams per liter Standard Deviation 9.06
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 57: Hemoglobin, n=6,3,22	-3.8 Grams per liter Standard Deviation 8.47	-2.7 Grams per liter Standard Deviation 11.15	-13.7 Grams per liter Standard Deviation 12.32
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 71: Hemoglobin, n=8,3,20	-4.1 Grams per liter Standard Deviation 10.38	-6.3 Grams per liter Standard Deviation 4.73	-21.2 Grams per liter Standard Deviation 11.61
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 85: Hemoglobin, n=7,3,22	-3.9 Grams per liter Standard Deviation 7.58	-10.7 Grams per liter Standard Deviation 6.11	-22.0 Grams per liter Standard Deviation 10.05
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 113: Hemoglobin, n=7,3,21	-5.0 Grams per liter Standard Deviation 8.43	-9.0 Grams per liter Standard Deviation 7.55	-21.3 Grams per liter Standard Deviation 10.49
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 155: Hemoglobin, n=7,3,20	-6.3 Grams per liter Standard Deviation 9.41	-7.3 Grams per liter Standard Deviation 6.03	-14.3 Grams per liter Standard Deviation 8.62
Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) Day 197: Hemoglobin, n=7,3,19	-4.1 Grams per liter Standard Deviation 8.88	-6.7 Grams per liter Standard Deviation 2.08	-5.8 Grams per liter Standard Deviation 6.58

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Hematology Parameter: Hematocrit Day 15: n=8,3,23	-0.0089 Proportion of red blood cells in blood Standard Deviation 0.02744	0.0127 Proportion of red blood cells in blood Standard Deviation 0.02203	-0.0035 Proportion of red blood cells in blood Standard Deviation 0.01771
Change From Baseline in Hematology Parameter: Hematocrit Day 29: n=8,3,23	-0.0023 Proportion of red blood cells in blood Standard Deviation 0.01955	-0.0027 Proportion of red blood cells in blood Standard Deviation 0.04234	-0.0141 Proportion of red blood cells in blood Standard Deviation 0.02486
Change From Baseline in Hematology Parameter: Hematocrit Day 43: n=8,3,22	-0.0049 Proportion of red blood cells in blood Standard Deviation 0.01788	-0.0057 Proportion of red blood cells in blood Standard Deviation 0.03564	-0.0271 Proportion of red blood cells in blood Standard Deviation 0.03187
Change From Baseline in Hematology Parameter: Hematocrit Day 57: n=6,3,22	-0.0092 Proportion of red blood cells in blood Standard Deviation 0.02500	-0.0120 Proportion of red blood cells in blood Standard Deviation 0.03274	-0.0444 Proportion of red blood cells in blood Standard Deviation 0.04224
Change From Baseline in Hematology Parameter: Hematocrit Day 71: n=8,3,20	-0.0146 Proportion of red blood cells in blood Standard Deviation 0.02870	-0.0217 Proportion of red blood cells in blood Standard Deviation 0.02329	-0.0637 Proportion of red blood cells in blood Standard Deviation 0.03983
Change From Baseline in Hematology Parameter: Hematocrit Day 85: n=7,3,22	-0.0151 Proportion of red blood cells in blood Standard Deviation 0.02591	-0.0300 Proportion of red blood cells in blood Standard Deviation 0.01803	-0.0688 Proportion of red blood cells in blood Standard Deviation 0.03265
Change From Baseline in Hematology Parameter: Hematocrit Day 113: n=7,3,20	-0.0141 Proportion of red blood cells in blood Standard Deviation 0.03007	-0.0323 Proportion of red blood cells in blood Standard Deviation 0.02822	-0.0602 Proportion of red blood cells in blood Standard Deviation 0.02839
Change From Baseline in Hematology Parameter: Hematocrit Day 155: n=7,3,17	-0.0164 Proportion of red blood cells in blood Standard Deviation 0.03169	-0.0263 Proportion of red blood cells in blood Standard Deviation 0.01626	-0.0349 Proportion of red blood cells in blood Standard Deviation 0.02482
Change From Baseline in Hematology Parameter: Hematocrit Day 197: n=7,3,15	-0.0111 Proportion of red blood cells in blood Standard Deviation 0.02634	-0.0193 Proportion of red blood cells in blood Standard Deviation 0.00981	-0.0125 Proportion of red blood cells in blood Standard Deviation 0.02252

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze the hematology parameter: MCH. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH) Day 15: n=8,3,23	-0.08 Picogram Standard Deviation 0.711	0.03 Picogram Standard Deviation 0.493	0.04 Picogram Standard Deviation 0.503
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH) Day 29: n=8,3,23	-0.24 Picogram Standard Deviation 0.616	0.37 Picogram Standard Deviation 0.709	-0.23 Picogram Standard Deviation 0.437
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH) Day 43: n=8,3,22	-0.23 Picogram Standard Deviation 0.807	-0.10 Picogram Standard Deviation 0.173	-0.41 Picogram Standard Deviation 0.450
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH) Day 57: n=6,3,22	-0.25 Picogram Standard Deviation 0.750	0.10 Picogram Standard Deviation 0.361	-0.39 Picogram Standard Deviation 0.493
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH) Day 71: n=8,3,20	0.18 Picogram Standard Deviation 0.945	0.17 Picogram Standard Deviation 0.379	-0.50 Picogram Standard Deviation 0.503
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH) Day 85: n=7,3,22	0.07 Picogram Standard Deviation 1.034	-0.30 Picogram Standard Deviation 0.755	-0.45 Picogram Standard Deviation 0.709
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH) Day 113: n=7,3,20	-0.06 Picogram Standard Deviation 0.808	0.87 Picogram Standard Deviation 0.513	-0.27 Picogram Standard Deviation 0.873
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH) Day 155: n=7,3,17	-0.16 Picogram Standard Deviation 0.637	0.90 Picogram Standard Deviation 0.200	0.04 Picogram Standard Deviation 1.180
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH) Day 197: n=7,3,15	-0.44 Picogram Standard Deviation 1.015	0.33 Picogram Standard Deviation 0.208	-0.23 Picogram Standard Deviation 1.285

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze the hematology parameters: MCV and MPV. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 15: MCV, n=8,3,23	-0.63 Femtoliter Standard Deviation 1.188	1.33 Femtoliter Standard Deviation 1.528	-0.39 Femtoliter Standard Deviation 1.725
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 29: MCV, n=8,3,23	0.38 Femtoliter Standard Deviation 1.188	0.33 Femtoliter Standard Deviation 1.155	-1.17 Femtoliter Standard Deviation 2.188
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 43: MCV, n=8,3,22	-0.38 Femtoliter Standard Deviation 2.326	-0.67 Femtoliter Standard Deviation 1.528	-1.86 Femtoliter Standard Deviation 1.583
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 57: MCV, n=6,3,22	-0.17 Femtoliter Standard Deviation 2.787	-1.00 Femtoliter Standard Deviation 0.000	-1.77 Femtoliter Standard Deviation 2.308
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 71: MCV, n=8,3,20	-0.13 Femtoliter Standard Deviation 3.441	-0.67 Femtoliter Standard Deviation 1.528	-1.60 Femtoliter Standard Deviation 2.722
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 85: MCV, n=7,3,22	-0.71 Femtoliter Standard Deviation 1.113	-0.67 Femtoliter Standard Deviation 0.577	-2.05 Femtoliter Standard Deviation 2.478
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 113: MCV, n=7,3,21	-0.29 Femtoliter Standard Deviation 2.563	1.00 Femtoliter Standard Deviation 1.732	0.00 Femtoliter Standard Deviation 3.225
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 155: MCV, n=7,3,20	-0.14 Femtoliter Standard Deviation 1.215	1.67 Femtoliter Standard Deviation 0.577	1.26 Femtoliter Standard Deviation 4.584
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 197: MCV, n=7,3,18	-1.29 Femtoliter Standard Deviation 1.799	0.67 Femtoliter Standard Deviation 2.082	-0.02 Femtoliter Standard Deviation 3.575
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 15: MPV, n=8,3,23	0.04 Femtoliter Standard Deviation 0.256	0.20 Femtoliter Standard Deviation 0.361	0.45 Femtoliter Standard Deviation 0.460
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 29: MPV, n=8,3,23	-0.04 Femtoliter Standard Deviation 0.378	0.47 Femtoliter Standard Deviation 0.764	0.29 Femtoliter Standard Deviation 0.630
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 43: MPV, n=7,3,22	-0.14 Femtoliter Standard Deviation 0.276	0.23 Femtoliter Standard Deviation 0.737	0.07 Femtoliter Standard Deviation 0.594
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 57: MPV, n=6,3,21	0.23 Femtoliter Standard Deviation 0.446	0.47 Femtoliter Standard Deviation 0.416	0.12 Femtoliter Standard Deviation 0.599
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 71: MPV, n=7,3,20	-0.21 Femtoliter Standard Deviation 0.393	0.23 Femtoliter Standard Deviation 0.231	-0.15 Femtoliter Standard Deviation 0.516
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 85: MPV, n=7,3,22	0.00 Femtoliter Standard Deviation 0.356	0.43 Femtoliter Standard Deviation 0.808	-0.11 Femtoliter Standard Deviation 0.462
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 113: MPV, n=7,3,19	-0.04 Femtoliter Standard Deviation 0.443	0.30 Femtoliter Standard Deviation 0.781	0.03 Femtoliter Standard Deviation 0.622
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 155: MPV, n=6,3,17	0.17 Femtoliter Standard Deviation 0.565	0.10 Femtoliter Standard Deviation 0.872	0.01 Femtoliter Standard Deviation 0.448
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) Day 197: MPV, n=7,3,15	-0.11 Femtoliter Standard Deviation 0.385	0.10 Femtoliter Standard Deviation 0.781	0.07 Femtoliter Standard Deviation 0.580

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze the hematology parameters: RBC count and reticulocyte count. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze the hematology parameter: RDW. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) Day 197: n=7,3,15	-0.16 Percentage of width Standard Deviation 1.286	-0.57 Percentage of width Standard Deviation 1.872	1.06 Percentage of width Standard Deviation 1.375
Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) Day 15: n=8,3,23	0.04 Percentage of width Standard Deviation 0.711	-0.27 Percentage of width Standard Deviation 1.050	-0.26 Percentage of width Standard Deviation 0.667
Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) Day 29: n=8,3,23	0.24 Percentage of width Standard Deviation 0.417	-0.53 Percentage of width Standard Deviation 1.704	-0.47 Percentage of width Standard Deviation 1.036
Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) Day 43: n=8,3,22	0.25 Percentage of width Standard Deviation 0.583	-0.97 Percentage of width Standard Deviation 1.650	-0.47 Percentage of width Standard Deviation 1.049
Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) Day 57: n=6,3,22	-0.02 Percentage of width Standard Deviation 0.578	-0.83 Percentage of width Standard Deviation 2.248	0.15 Percentage of width Standard Deviation 1.331
Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) Day 71: n=8,3,20	0.04 Percentage of width Standard Deviation 0.725	-0.23 Percentage of width Standard Deviation 2.570	0.96 Percentage of width Standard Deviation 2.040
Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) Day 85: n=7,3,22	-0.04 Percentage of width Standard Deviation 0.663	-0.20 Percentage of width Standard Deviation 2.307	1.67 Percentage of width Standard Deviation 1.792
Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) Day 113: n=7,3,20	0.26 Percentage of width Standard Deviation 0.748	0.73 Percentage of width Standard Deviation 1.950	4.24 Percentage of width Standard Deviation 2.737
Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) Day 155: n=7,3,17	-0.09 Percentage of width Standard Deviation 0.771	0.10 Percentage of width Standard Deviation 1.916	2.86 Percentage of width Standard Deviation 1.636

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze the hematology parameter: Reticulocyte Production Index. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Reticulocyte Production Index (RPI) was calculated as 'Reticulocyte Production Index = Reticulocyte Count (percent \[%\]) multiply by (x) (hematocrit \[%\] divided by \[/\] 45) x 1/ reticulocyte maturation time'.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Reticulocyte Production Index Day 15: n=8,3,23	0.2009 Unitless Standard Deviation 0.49644	-0.1787 Unitless Standard Deviation 0.53867	-0.2757 Unitless Standard Deviation 0.20191
Change From Baseline in Reticulocyte Production Index Day 29: n=8,3,23	0.0391 Unitless Standard Deviation 0.09687	-0.2397 Unitless Standard Deviation 0.51850	-0.2460 Unitless Standard Deviation 0.35460
Change From Baseline in Reticulocyte Production Index Day 43: n=8,3,22	-0.0691 Unitless Standard Deviation 0.11447	-0.3437 Unitless Standard Deviation 0.55192	-0.2342 Unitless Standard Deviation 0.34389
Change From Baseline in Reticulocyte Production Index Day 57: n=6,3,22	-0.0763 Unitless Standard Deviation 0.13476	-0.2877 Unitless Standard Deviation 0.48015	-0.1933 Unitless Standard Deviation 0.32326
Change From Baseline in Reticulocyte Production Index Day 71: n=8,3,19	0.0154 Unitless Standard Deviation 0.24560	-0.4643 Unitless Standard Deviation 0.13444	-0.1344 Unitless Standard Deviation 0.29111
Change From Baseline in Reticulocyte Production Index Day 85: n=7,3,22	-0.0831 Unitless Standard Deviation 0.14906	-0.4530 Unitless Standard Deviation 0.48914	-0.0112 Unitless Standard Deviation 0.32736
Change From Baseline in Reticulocyte Production Index Day 113: n=7,3,20	-0.1006 Unitless Standard Deviation 0.21168	-0.2633 Unitless Standard Deviation 0.29016	0.2826 Unitless Standard Deviation 0.33003
Change From Baseline in Reticulocyte Production Index Day 155: n=7,3,17	-0.0033 Unitless Standard Deviation 0.24087	-0.4720 Unitless Standard Deviation 0.24857	0.1105 Unitless Standard Deviation 0.28718
Change From Baseline in Reticulocyte Production Index Day 197: n=7,3,15	-0.0296 Unitless Standard Deviation 0.11222	-0.5693 Unitless Standard Deviation 0.43160	0.0087 Unitless Standard Deviation 0.16995

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze the hematology parameter: reticulocytes. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline Hematology Parameter: Reticulocytes Day 85: n=7,3,22	-0.0007 Percentage of reticulocytes Standard Deviation 0.00138	-0.0043 Percentage of reticulocytes Standard Deviation 0.00651	0.0065 Percentage of reticulocytes Standard Deviation 0.00647
Change From Baseline Hematology Parameter: Reticulocytes Day 15: n=8,3,23	0.0026 Percentage of reticulocytes Standard Deviation 0.00534	-0.0053 Percentage of reticulocytes Standard Deviation 0.00551	-0.0037 Percentage of reticulocytes Standard Deviation 0.00236
Change From Baseline Hematology Parameter: Reticulocytes Day 29: n=8,3,23	0.0001 Percentage of reticulocytes Standard Deviation 0.00155	-0.0040 Percentage of reticulocytes Standard Deviation 0.00265	-0.0030 Percentage of reticulocytes Standard Deviation 0.00423
Change From Baseline Hematology Parameter: Reticulocytes Day 43: n=8,3,22	-0.0008 Percentage of reticulocytes Standard Deviation 0.00128	-0.0057 Percentage of reticulocytes Standard Deviation 0.00611	-0.0021 Percentage of reticulocytes Standard Deviation 0.00389
Change From Baseline Hematology Parameter: Reticulocytes Day 57: n=6,3,22	-0.0012 Percentage of reticulocytes Standard Deviation 0.00214	-0.0023 Percentage of reticulocytes Standard Deviation 0.00551	0.0004 Percentage of reticulocytes Standard Deviation 0.00422
Change From Baseline Hematology Parameter: Reticulocytes Day 71: n=8,3,19	0.0014 Percentage of reticulocytes Standard Deviation 0.00325	-0.0027 Percentage of reticulocytes Standard Deviation 0.00551	0.0037 Percentage of reticulocytes Standard Deviation 0.00625
Change From Baseline Hematology Parameter: Reticulocytes Day 113: n=7,3,20	-0.0011 Percentage of reticulocytes Standard Deviation 0.00219	0.0013 Percentage of reticulocytes Standard Deviation 0.00702	0.0121 Percentage of reticulocytes Standard Deviation 0.00704
Change From Baseline Hematology Parameter: Reticulocytes Day 155: n=7,3,17	0.0006 Percentage of reticulocytes Standard Deviation 0.00162	-0.0027 Percentage of reticulocytes Standard Deviation 0.00603	0.0054 Percentage of reticulocytes Standard Deviation 0.00405
Change From Baseline Hematology Parameter: Reticulocytes Day 197: n=7,3,15	0.0001 Percentage of reticulocytes Standard Deviation 0.00157	-0.0063 Percentage of reticulocytes Standard Deviation 0.00924	0.0005 Percentage of reticulocytes Standard Deviation 0.00233

PRIMARY outcome

Timeframe: Up to Day 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected for analysis of clinical chemistry parameters. PCI ranges were low: \<30 grams per liter (g/L) (albumin), high: \>44.2 micromoles per liter (µmol/L) increase from Baseline (creatinine), low: \<3 or high: \>9 mmol/L (glucose), low: \<3 or high: \>5.5 mmol/L (potassium), and low: \<130 or high: \>150 mmol/L (sodium). Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there was no change in their category. Participants whose laboratory value category was unchanged (e.g. High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add up to 100%.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Albumin: To Low	0 Participants	0 Participants	0 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Albumin: To within Range or No Change	8 Participants	3 Participants	23 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Albumin: To High	0 Participants	0 Participants	0 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Creatinine: To Low	0 Participants	0 Participants	0 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Creatinine: To within Range or No Change	8 Participants	3 Participants	23 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Creatinine: To High	0 Participants	0 Participants	0 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Glucose: To Low	0 Participants	0 Participants	1 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Glucose: To within Range or No Change	8 Participants	2 Participants	19 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Glucose: To High	0 Participants	1 Participants	3 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Potassium: To Low	0 Participants	0 Participants	0 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Potassium: To within Range or No Change	7 Participants	3 Participants	22 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Potassium: To High	1 Participants	0 Participants	1 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Sodium: To Low	0 Participants	0 Participants	0 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Sodium: To within Range or No Change	8 Participants	3 Participants	23 Participants
Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Sodium: To High	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze chemistry parameter: total protein. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Chemistry Parameter: Total Protein Day 15: n=7,2,23	1.0 Grams per liter Standard Deviation 3.06	0.5 Grams per liter Standard Deviation 4.95	0.4 Grams per liter Standard Deviation 3.56
Change From Baseline in Chemistry Parameter: Total Protein Day 29: n=8,2,23	-0.1 Grams per liter Standard Deviation 3.14	-1.0 Grams per liter Standard Deviation 5.66	0.7 Grams per liter Standard Deviation 2.86
Change From Baseline in Chemistry Parameter: Total Protein Day 43: n=8,3,22	-0.1 Grams per liter Standard Deviation 2.36	-0.3 Grams per liter Standard Deviation 2.08	-0.5 Grams per liter Standard Deviation 3.52
Change From Baseline in Chemistry Parameter: Total Protein Day 57: n=7,3,22	1.3 Grams per liter Standard Deviation 2.29	1.3 Grams per liter Standard Deviation 2.08	-0.5 Grams per liter Standard Deviation 3.65
Change From Baseline in Chemistry Parameter: Total Protein Day 71: n=8,3,21	-0.1 Grams per liter Standard Deviation 3.56	0.7 Grams per liter Standard Deviation 1.15	-1.1 Grams per liter Standard Deviation 4.44
Change From Baseline in Chemistry Parameter: Total Protein Day 85: n=8,3,22	0.3 Grams per liter Standard Deviation 1.39	0.0 Grams per liter Standard Deviation 2.00	0.3 Grams per liter Standard Deviation 3.71
Change From Baseline in Chemistry Parameter: Total Protein Day 113: n=7,3,20	-0.9 Grams per liter Standard Deviation 2.61	1.7 Grams per liter Standard Deviation 0.58	0.2 Grams per liter Standard Deviation 4.06
Change From Baseline in Chemistry Parameter: Total Protein Day 155: n=7,3,18	-1.3 Grams per liter Standard Deviation 1.25	3.0 Grams per liter Standard Deviation 7.21	-0.1 Grams per liter Standard Deviation 4.59
Change From Baseline in Chemistry Parameter: Total Protein Day 197: n=7,3,19	2.3 Grams per liter Standard Deviation 3.90	2.3 Grams per liter Standard Deviation 3.51	1.5 Grams per liter Standard Deviation 5.00

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze chemistry parameters: ALP, ALT, AST and LDH. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze chemistry parameters: total bilirubin and direct bilirubin. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose) and Day 85

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze chemistry parameters: cholesterol, direct HDL cholesterol, LDL cholesterol and triglycerides. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from post-dose visit value.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=22 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Chemistry Parameters: Cholesterol, Direct High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, Triglycerides Cholesterol: n=8,3,22	-0.125 Millimoles per liter Standard Deviation 0.7474	0.067 Millimoles per liter Standard Deviation 0.1258	0.450 Millimoles per liter Standard Deviation 0.5780
Change From Baseline in Chemistry Parameters: Cholesterol, Direct High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, Triglycerides Direct HDL Cholesterol: n=7,3,22	-0.093 Millimoles per liter Standard Deviation 0.1718	-0.033 Millimoles per liter Standard Deviation 0.0289	-0.036 Millimoles per liter Standard Deviation 0.2989
Change From Baseline in Chemistry Parameters: Cholesterol, Direct High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, Triglycerides LDL Cholesterol: n=7,3,21	-0.091 Millimoles per liter Standard Deviation 0.7376	0.110 Millimoles per liter Standard Deviation 0.1200	0.274 Millimoles per liter Standard Deviation 0.5011
Change From Baseline in Chemistry Parameters: Cholesterol, Direct High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, Triglycerides Triglycerides: n=8,3,22	0.025 Millimoles per liter Standard Deviation 0.3427	-0.020 Millimoles per liter Standard Deviation 0.0800	0.535 Millimoles per liter Standard Deviation 0.8036

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze chemistry parameters: corrected calcium and urea. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected to analyze chemistry parameter: estimated glomerular filtration rate. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate Day 15: n=7,2,23	-6.4180 Milliliter/minute/1.73 square meter Standard Deviation 10.28099	1.7630 Milliliter/minute/1.73 square meter Standard Deviation 1.28693	-0.7528 Milliliter/minute/1.73 square meter Standard Deviation 9.25789
Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate Day 29: n=8,2,23	-4.3085 Milliliter/minute/1.73 square meter Standard Deviation 8.34077	-2.7765 Milliliter/minute/1.73 square meter Standard Deviation 9.78424	-1.5543 Milliliter/minute/1.73 square meter Standard Deviation 9.55847
Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate Day 43: n=8,3,22	-0.4780 Milliliter/minute/1.73 square meter Standard Deviation 9.34592	-4.3223 Milliliter/minute/1.73 square meter Standard Deviation 3.88914	-3.4266 Milliliter/minute/1.73 square meter Standard Deviation 6.99189
Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate Day 57: n=7,3,22	1.3446 Milliliter/minute/1.73 square meter Standard Deviation 7.12100	2.6893 Milliliter/minute/1.73 square meter Standard Deviation 5.61068	-5.1256 Milliliter/minute/1.73 square meter Standard Deviation 7.41957
Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate Day 71: n=8,3,21	-0.4405 Milliliter/minute/1.73 square meter Standard Deviation 12.50899	-0.9993 Milliliter/minute/1.73 square meter Standard Deviation 5.98467	-2.5432 Milliliter/minute/1.73 square meter Standard Deviation 7.12712
Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate Day 85: n=8,3,22	-1.0010 Milliliter/minute/1.73 square meter Standard Deviation 8.15284	-7.1513 Milliliter/minute/1.73 square meter Standard Deviation 6.77426	-5.1038 Milliliter/minute/1.73 square meter Standard Deviation 8.90164
Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate Day 113: n=7,3,20	-2.7351 Milliliter/minute/1.73 square meter Standard Deviation 12.23546	-0.2900 Milliliter/minute/1.73 square meter Standard Deviation 6.19990	-8.5267 Milliliter/minute/1.73 square meter Standard Deviation 7.71222
Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate Day 155: n=7,3,20	-0.9239 Milliliter/minute/1.73 square meter Standard Deviation 13.25672	-3.9510 Milliliter/minute/1.73 square meter Standard Deviation 5.74000	-4.2795 Milliliter/minute/1.73 square meter Standard Deviation 9.19612
Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate Day 197: n=7,3,21	-4.2733 Milliliter/minute/1.73 square meter Standard Deviation 15.36640	-7.7100 Milliliter/minute/1.73 square meter Standard Deviation 8.47159	-2.7185 Milliliter/minute/1.73 square meter Standard Deviation 8.91665

PRIMARY outcome

Timeframe: Up to Day 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed.

Urine samples were collected for the assessment of potential of hydrogen, specific gravity, glucose, ketones, occult blood and protein by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters: potential of hydrogen, specific gravity, glucose, ketones, occult blood and protein were categorized as 'any increase from Baseline', which imply any increase in their concentrations in the urine sample. Only participants with emergent worst case any increase from Baseline values are presented.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Number of Participants With Emergent Worst Case Urinalysis Results by Dipstick Ketones, Any increase	1 Participants	0 Participants	4 Participants
Number of Participants With Emergent Worst Case Urinalysis Results by Dipstick Potential of hydrogen, Any increase	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Worst Case Urinalysis Results by Dipstick Specific gravity, Any increase	0 Participants	0 Participants	3 Participants
Number of Participants With Emergent Worst Case Urinalysis Results by Dipstick Glucose, Any increase	0 Participants	0 Participants	0 Participants
Number of Participants With Emergent Worst Case Urinalysis Results by Dipstick Occult blood, Any increase	2 Participants	0 Participants	3 Participants
Number of Participants With Emergent Worst Case Urinalysis Results by Dipstick Protein, Any increase	1 Participants	0 Participants	4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose) and up to Day 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed.

Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) were measured in a seated or semi-supine position after 5 minutes of rest using a completely automated device. PCI ranges were: SBP (increase or decrease from Baseline of \>=40 millimeter of mercury \[mmHg\]), DBP (increase or decrease from Baseline of \>=20 mmHg), and HR (increase or decrease from Baseline of \>=30 beats per minute). Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Number of Participants With Vital Signs Relative to Change From Baseline by Potential Clinical Importance (PCI) Criteria DBP: Decrease >=20	2 Participants	0 Participants	2 Participants
Number of Participants With Vital Signs Relative to Change From Baseline by Potential Clinical Importance (PCI) Criteria DBP: Increase >=20	0 Participants	0 Participants	1 Participants
Number of Participants With Vital Signs Relative to Change From Baseline by Potential Clinical Importance (PCI) Criteria SBP: Decrease >=40	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Relative to Change From Baseline by Potential Clinical Importance (PCI) Criteria SBP: Increase >=40	0 Participants	0 Participants	2 Participants
Number of Participants With Vital Signs Relative to Change From Baseline by Potential Clinical Importance (PCI) Criteria HR: Decrease >=30	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Relative to Change From Baseline by Potential Clinical Importance (PCI) Criteria HR: Increase >=30	1 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Body temperature was measured in a seated or semi-supine position after 5 minutes of rest. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Body Temperature Day 15: n=8,3,23	0.037 Degrees Celsius Standard Deviation 0.4689	0.400 Degrees Celsius Standard Deviation 0.4359	0.117 Degrees Celsius Standard Deviation 0.3833
Change From Baseline in Body Temperature Day 29: n=8,3,23	0.037 Degrees Celsius Standard Deviation 0.3889	0.467 Degrees Celsius Standard Deviation 0.6807	0.130 Degrees Celsius Standard Deviation 0.3470
Change From Baseline in Body Temperature Day 43: n=8,3,23	0.012 Degrees Celsius Standard Deviation 0.4121	0.033 Degrees Celsius Standard Deviation 0.4163	0.039 Degrees Celsius Standard Deviation 0.4197
Change From Baseline in Body Temperature Day 57: n=7,3,22	0.100 Degrees Celsius Standard Deviation 0.2449	0.133 Degrees Celsius Standard Deviation 0.3215	0.177 Degrees Celsius Standard Deviation 0.4253
Change From Baseline in Body Temperature Day 71: n=8,3,21	-0.112 Degrees Celsius Standard Deviation 0.5303	0.267 Degrees Celsius Standard Deviation 0.5132	0.186 Degrees Celsius Standard Deviation 0.4328
Change From Baseline in Body Temperature Day 85: n=8,3,22	0.012 Degrees Celsius Standard Deviation 0.3563	0.467 Degrees Celsius Standard Deviation 0.5859	-0.023 Degrees Celsius Standard Deviation 0.3854
Change From Baseline in Body Temperature Day 113: n=7,3,20	-0.257 Degrees Celsius Standard Deviation 0.3505	0.400 Degrees Celsius Standard Deviation 0.6245	0.100 Degrees Celsius Standard Deviation 0.4952
Change From Baseline in Body Temperature Day 155: n=7,3,17	-0.257 Degrees Celsius Standard Deviation 0.3409	0.167 Degrees Celsius Standard Deviation 0.5033	0.118 Degrees Celsius Standard Deviation 0.6054
Change From Baseline in Body Temperature Day 197: n=7,3,17	-0.143 Degrees Celsius Standard Deviation 0.4860	0.267 Degrees Celsius Standard Deviation 0.4933	0.212 Degrees Celsius Standard Deviation 0.5122

PRIMARY outcome

Timeframe: Up to Day 57

Population: Safety Population. Only those participants with data available at the specified time points were analyzed.

Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings Abnormal- not clinically significant	3 Participants	2 Participants	10 Participants
Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings Abnormal- clinically significant	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Days 1, 15, 29, 57, 85, 113, 155 and 197

Population: PK Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK2330811. Pharmacokinetic (PK) Population was defined as participants in the 'Safety' population who received an active dose and for whom a PK sample was obtained and analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=24 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Plasma Concentrations of GSK2330811 Day 1: n=3,24	NA Nanogram per milliliter Standard Deviation NA Mean and standard deviation could not be calculated due to high proportion of non-quantifiable (NQ) values (more than \[\>\] 30 percent \[%\] of values were imputed).	0.0 Nanogram per milliliter Standard Deviation NA Mean and standard deviation could not be calculated due to high proportion of NQ values (\>30% of values were imputed).	—
Plasma Concentrations of GSK2330811 Day 15: n=3,23	5510.7 Nanogram per milliliter Standard Deviation 2455.19	16197.9 Nanogram per milliliter Standard Deviation 6354.54	—
Plasma Concentrations of GSK2330811 Day 29: n=3,23	7782.3 Nanogram per milliliter Standard Deviation 1563.04	23407.0 Nanogram per milliliter Standard Deviation 8830.49	—
Plasma Concentrations of GSK2330811 Day 57: n=3,22	9868.7 Nanogram per milliliter Standard Deviation 818.51	32645.7 Nanogram per milliliter Standard Deviation 15225.01	—
Plasma Concentrations of GSK2330811 Day 85: n=3,22	10993.0 Nanogram per milliliter Standard Deviation 717.89	29254.4 Nanogram per milliliter Standard Deviation 16911.55	—
Plasma Concentrations of GSK2330811 Day 113: n=3,20	4123.0 Nanogram per milliliter Standard Deviation 420.29	11087.1 Nanogram per milliliter Standard Deviation 7661.76	—
Plasma Concentrations of GSK2330811 Day 155: n=3,16	580.0 Nanogram per milliliter Standard Deviation 408.47	2892.9 Nanogram per milliliter Standard Deviation 4093.61	—
Plasma Concentrations of GSK2330811 Day 197: n=3,17	114.0 Nanogram per milliliter Standard Deviation NA Mean and standard deviation could not be calculated due to high proportion of NQ values (\>30% of values were imputed).	729.2 Nanogram per milliliter Standard Deviation 841.17	—

SECONDARY outcome

Timeframe: Days 1, 15, 29, 57, 85, 113, 155 and 197

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at the indicated time points for PK analysis of GSK2330811.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=22 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Concentration at the End of the Dosing Interval (Ctrough) of GSK2330811	10993.0 Nanogram per milliliter Standard Deviation 717.89	29254.4 Nanogram per milliliter Standard Deviation 16911.55	—

SECONDARY outcome

Timeframe: Days 1, 15, 29, 57, 85, 113, 155 and 197

Population: PK Population. Only those participants with data available at the specified time points were analyzed. CL/F was estimated based on population PK modelling on the combination of data of participants dosed with GSK2330811, as it was more appropriate due to limited dose range (100 mg and 300 mg).

Blood samples were collected at the indicated time points for PK analysis of GSK2330811. Data was analyzed by population pharmacokinetic methods using a non-linear mixed-effects modelling approach.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Apparent Clearance (CL/F) of GSK2330811	0.0147 Liter per hour Interval 0.0132 to 0.0163	—	—

SECONDARY outcome

Timeframe: Days 1, 15, 29, 57, 85, 113, 155 and 197

Population: PK Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at the indicated time points for PK analysis of GSK2330811. Data was analyzed by population pharmacokinetic methods using a non-linear mixed-effects modelling approach.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Apparent Volume of Distribution (Vss/F) of GSK2330811	3.25 Liter The PK parameters were calculated by fitting a population PK model using the combined data of participants dosed with 100 mg and 300 mg of GSK2330811. Since a minimal model was utilized, the Vss/F value was fixed to a plasma physiological value obtained from the literature. Hence, a confidence interval cannot be provided for this parameter.	—	—

SECONDARY outcome

Timeframe: Days 1, 15, 29, 57, 85, 113, 155 and 197

Population: Per Protocol Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected at indicated timepoints for analysis of total OSM levels in serum. Per Protocol Population comprised of participants in the 'Safety' population who complied with the protocol.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Serum Level of Total Oncostatin M (OSM) Day 1: n=8,3,22	22.110 Picogram per milliliter Interval 13.08 to 57.4	30.590 Picogram per milliliter Interval 6.19 to 38.71	27.455 Picogram per milliliter Interval 16.93 to 81.71
Serum Level of Total Oncostatin M (OSM) Day 15: n=8,3,23	28.175 Picogram per milliliter Interval 18.07 to 57.48	576.850 Picogram per milliliter Interval 417.28 to 696.18	721.020 Picogram per milliliter Interval 496.63 to 1482.91
Serum Level of Total Oncostatin M (OSM) Day 29: n=8,3,23	26.210 Picogram per milliliter Interval 12.84 to 48.82	499.540 Picogram per milliliter Interval 487.14 to 635.94	974.220 Picogram per milliliter Interval 398.94 to 2500.01
Serum Level of Total Oncostatin M (OSM) Day 57: n=7,3,22	34.700 Picogram per milliliter Interval 13.4 to 43.94	651.710 Picogram per milliliter Interval 554.93 to 971.25	1211.570 Picogram per milliliter Interval 636.83 to 2350.65
Serum Level of Total Oncostatin M (OSM) Day 85: n=8,3,22	17.275 Picogram per milliliter Interval 14.38 to 66.28	613.290 Picogram per milliliter Interval 555.09 to 1229.71	1357.645 Picogram per milliliter Interval 542.85 to 2500.01
Serum Level of Total Oncostatin M (OSM) Day 113: n=7,3,20	23.350 Picogram per milliliter Interval 8.42 to 81.11	687.810 Picogram per milliliter Interval 419.04 to 935.76	1044.650 Picogram per milliliter Interval 186.06 to 2378.21
Serum Level of Total Oncostatin M (OSM) Day 155: n=7,3,17	23.850 Picogram per milliliter Interval 13.13 to 43.07	206.900 Picogram per milliliter Interval 143.55 to 363.62	359.340 Picogram per milliliter Interval 58.13 to 1097.7
Serum Level of Total Oncostatin M (OSM) Day 197: n=7,3,17	28.800 Picogram per milliliter Interval 19.58 to 36.13	54.290 Picogram per milliliter Interval 40.96 to 137.88	142.830 Picogram per milliliter Interval 28.82 to 607.09

SECONDARY outcome

Timeframe: Days 1, 15, 29, 57, 85, 113, 155 and 197

Population: Per Protocol Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Blood samples were collected at indicated timepoints for analysis of free OSM levels in serum.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Serum Level of Free OSM Day 1: n=8,3,22	19.72 Picogram per milliliter Interval 8.3 to 45.3	28.93 Picogram per milliliter Interval 4.5 to 36.8	20.74 Picogram per milliliter Interval 8.8 to 56.0
Serum Level of Free OSM Day 15: n=8,3,23	23.85 Picogram per milliliter Interval 11.7 to 40.7	0.73 Picogram per milliliter Interval 0.73 to 0.73	0.73 Picogram per milliliter Interval 0.73 to 0.73
Serum Level of Free OSM Day 29: n=8,3,23	19.35 Picogram per milliliter Interval 4.5 to 37.1	0.73 Picogram per milliliter Interval 0.73 to 0.73	0.73 Picogram per milliliter Interval 0.73 to 0.73
Serum Level of Free OSM Day 57: n=7,3,22	27.62 Picogram per milliliter Interval 6.1 to 35.9	0.73 Picogram per milliliter Interval 0.73 to 0.73	0.73 Picogram per milliliter Interval 0.73 to 0.73
Serum Level of Free OSM Day 85: n=8,3,22	12.37 Picogram per milliliter Interval 5.9 to 47.6	0.73 Picogram per milliliter Interval 0.73 to 0.73	0.73 Picogram per milliliter Interval 0.73 to 0.73
Serum Level of Free OSM Day 113: n=7,3,20	16.78 Picogram per milliliter Interval 5.7 to 58.5	0.73 Picogram per milliliter Interval 0.73 to 0.73	0.73 Picogram per milliliter Interval 0.73 to 0.73
Serum Level of Free OSM Day 155: n=7,3,17	14.54 Picogram per milliliter Interval 7.3 to 32.7	0.73 Picogram per milliliter Interval 0.73 to 0.73	0.73 Picogram per milliliter Interval 0.7 to 1.7
Serum Level of Free OSM Day 197: n=7,3,17	18.43 Picogram per milliliter Interval 12.2 to 23.5	0.73 Picogram per milliliter Interval 0.73 to 0.73	0.73 Picogram per milliliter Interval 0.7 to 2.7

SECONDARY outcome

Timeframe: Days 1, 15, 57, 85 and 197

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Serum samples were collected for the determination of anti-GSK2330811 antibodies (ADA) using a binding antibody detection assay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that were confirmed positive in the confirmation assay were reported as 'positive'.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Number of Participants With Positive Anti-GSK2330811 Antibodies Day 1: n=8,3,23	0 Participants	0 Participants	3 Participants
Number of Participants With Positive Anti-GSK2330811 Antibodies Day 15: n=8,3,23	0 Participants	0 Participants	1 Participants
Number of Participants With Positive Anti-GSK2330811 Antibodies Day 57: n=7,3,22	0 Participants	0 Participants	2 Participants
Number of Participants With Positive Anti-GSK2330811 Antibodies Day 85: n=8,3,22	0 Participants	0 Participants	1 Participants
Number of Participants With Positive Anti-GSK2330811 Antibodies Day 197: n=7,3,17	0 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

GSK2330811 100 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

GSK2330811 300 mg

Serious events: 2 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=8 participants at risk Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 participants at risk Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=24 participants at risk Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Cardiac disorders Atrial fibrillation	0.00% 0/8 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	0.00% 0/3 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	4.2% 1/24 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.
Cardiac disorders Pericarditis	0.00% 0/8 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	0.00% 0/3 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	4.2% 1/24 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.
Infections and infestations Infected skin ulcer	12.5% 1/8 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	0.00% 0/3 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	0.00% 0/24 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/8 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	0.00% 0/3 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	4.2% 1/24 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.00% 0/8 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	0.00% 0/3 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	4.2% 1/24 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.
Vascular disorders Hypotension	0.00% 0/8 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	0.00% 0/3 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.	4.2% 1/24 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.

Other adverse events

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

Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 15: RBC count, n=8,3,23	-0.05 Tera cells per liter Standard Deviation 0.321	0.07 Tera cells per liter Standard Deviation 0.208	-0.01 Tera cells per liter Standard Deviation 0.205
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 29: RBC count, n=8,3,23	-0.03 Tera cells per liter Standard Deviation 0.225	-0.07 Tera cells per liter Standard Deviation 0.404	-0.11 Tera cells per liter Standard Deviation 0.275
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 43: RBC count, n=8,3,22	-0.03 Tera cells per liter Standard Deviation 0.238	-0.07 Tera cells per liter Standard Deviation 0.321	-0.22 Tera cells per liter Standard Deviation 0.331
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 57: RBC count, n=6,3,22	-0.07 Tera cells per liter Standard Deviation 0.288	-0.10 Tera cells per liter Standard Deviation 0.361	-0.42 Tera cells per liter Standard Deviation 0.464
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 71: RBC count, n=8,3,20	-0.13 Tera cells per liter Standard Deviation 0.396	-0.23 Tera cells per liter Standard Deviation 0.208	-0.66 Tera cells per liter Standard Deviation 0.406
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 85: RBC count, n=7,3,22	-0.10 Tera cells per liter Standard Deviation 0.311	-0.33 Tera cells per liter Standard Deviation 0.208	-0.68 Tera cells per liter Standard Deviation 0.343
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 113: RBC count, n=7,3,20	-0.13 Tera cells per liter Standard Deviation 0.350	-0.40 Tera cells per liter Standard Deviation 0.265	-0.68 Tera cells per liter Standard Deviation 0.361
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 155: RBC count, n=7,3,17	-0.17 Tera cells per liter Standard Deviation 0.330	-0.37 Tera cells per liter Standard Deviation 0.252	-0.47 Tera cells per liter Standard Deviation 0.264
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 197: RBC count, n=7,3,15	-0.04 Tera cells per liter Standard Deviation 0.282	-0.23 Tera cells per liter Standard Deviation 0.058	-0.15 Tera cells per liter Standard Deviation 0.160
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 15: Reticulocyte count, n=8,3,23	0.0109 Tera cells per liter Standard Deviation 0.02401	-0.0207 Tera cells per liter Standard Deviation 0.02463	-0.0160 Tera cells per liter Standard Deviation 0.00964
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 29: Reticulocyte count, n=8,3,23	-0.0001 Tera cells per liter Standard Deviation 0.00543	-0.0169 Tera cells per liter Standard Deviation 0.00911	-0.0132 Tera cells per liter Standard Deviation 0.01784
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 43: Reticulocyte count, n=8,3,22	-0.0032 Tera cells per liter Standard Deviation 0.00554	-0.0228 Tera cells per liter Standard Deviation 0.02303	-0.0109 Tera cells per liter Standard Deviation 0.01699
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 57: Reticulocyte count, n=6,3,22	-0.0058 Tera cells per liter Standard Deviation 0.00638	-0.0091 Tera cells per liter Standard Deviation 0.02177	-0.0031 Tera cells per liter Standard Deviation 0.01656
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 71: Reticulocyte count, n=8,3,19	0.0026 Tera cells per liter Standard Deviation 0.01261	-0.0125 Tera cells per liter Standard Deviation 0.01878	0.0065 Tera cells per liter Standard Deviation 0.01934
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 85: Reticulocyte count, n=7,3,22	-0.0044 Tera cells per liter Standard Deviation 0.00539	-0.0209 Tera cells per liter Standard Deviation 0.02471	0.0152 Tera cells per liter Standard Deviation 0.02006
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 113: Reticulocyte count, n=7,3,20	-0.0064 Tera cells per liter Standard Deviation 0.01030	0.0012 Tera cells per liter Standard Deviation 0.02944	0.0356 Tera cells per liter Standard Deviation 0.02009
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 155: Reticulocyte count, n=7,3,17	0.0006 Tera cells per liter Standard Deviation 0.00623	-0.0157 Tera cells per liter Standard Deviation 0.02263	0.0158 Tera cells per liter Standard Deviation 0.01340
Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count, Reticulocyte Count Day 197: Reticulocyte count, n=7,3,16	0.0003 Tera cells per liter Standard Deviation 0.00550	-0.0285 Tera cells per liter Standard Deviation 0.03458	0.0017 Tera cells per liter Standard Deviation 0.01003

Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 15: ALP, n=7,2,23	-1.3 International units per liter Standard Deviation 10.53	-1.0 International units per liter Standard Deviation 4.24	0.6 International units per liter Standard Deviation 5.67
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 29: ALP, n=8,2,23	-2.3 International units per liter Standard Deviation 7.89	4.5 International units per liter Standard Deviation 6.36	-1.1 International units per liter Standard Deviation 10.94
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 43: ALP, n=8,3,22	-4.4 International units per liter Standard Deviation 12.36	0.7 International units per liter Standard Deviation 7.51	-1.1 International units per liter Standard Deviation 9.00
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 57: ALP, n=7,3,22	-5.0 International units per liter Standard Deviation 13.23	3.3 International units per liter Standard Deviation 9.07	1.0 International units per liter Standard Deviation 7.55
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 71: ALP, n=8,3,21	-3.5 International units per liter Standard Deviation 10.94	1.3 International units per liter Standard Deviation 1.53	-3.0 International units per liter Standard Deviation 11.52
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 85: ALP, n=8,3,22	-2.4 International units per liter Standard Deviation 11.96	-2.3 International units per liter Standard Deviation 4.93	-3.0 International units per liter Standard Deviation 11.65
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 113: ALP, n=7,3,20	-1.3 International units per liter Standard Deviation 4.99	-2.3 International units per liter Standard Deviation 4.93	-6.3 International units per liter Standard Deviation 8.15
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 155: ALP, n=7,3,19	-8.4 International units per liter Standard Deviation 15.88	-3.3 International units per liter Standard Deviation 5.69	-5.4 International units per liter Standard Deviation 9.84
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 197: ALP, n=7,3,19	-3.6 International units per liter Standard Deviation 12.16	-4.0 International units per liter Standard Deviation 6.93	-2.1 International units per liter Standard Deviation 11.03
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 15: ALT, n=7,2,23	-0.4 International units per liter Standard Deviation 2.70	0.0 International units per liter Standard Deviation 1.41	1.6 International units per liter Standard Deviation 3.85
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 29: ALT, n=8,2,23	0.6 International units per liter Standard Deviation 1.85	-2.0 International units per liter Standard Deviation 2.83	3.3 International units per liter Standard Deviation 9.58
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 43: ALT, n=8,3,22	1.3 International units per liter Standard Deviation 3.15	4.0 International units per liter Standard Deviation 6.08	3.1 International units per liter Standard Deviation 10.70
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 57: ALT, n=7,3,22	-1.6 International units per liter Standard Deviation 1.27	2.0 International units per liter Standard Deviation 4.58	3.7 International units per liter Standard Deviation 10.03
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 71: ALT, n=8,3,21	0.3 International units per liter Standard Deviation 2.82	3.0 International units per liter Standard Deviation 6.24	0.0 International units per liter Standard Deviation 2.67
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 85: ALT, n=8,3,22	-1.5 International units per liter Standard Deviation 3.89	-0.3 International units per liter Standard Deviation 2.52	0.4 International units per liter Standard Deviation 4.27
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 113: ALT, n=7,3,20	-1.4 International units per liter Standard Deviation 5.13	4.7 International units per liter Standard Deviation 8.14	0.2 International units per liter Standard Deviation 3.18
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 155: ALT, n=7,3,18	-2.6 International units per liter Standard Deviation 6.65	1.0 International units per liter Standard Deviation 1.00	0.9 International units per liter Standard Deviation 3.95
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 197: ALT, n=7,3,21	3.6 International units per liter Standard Deviation 3.87	-0.3 International units per liter Standard Deviation 2.52	2.4 International units per liter Standard Deviation 4.69
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 15: AST, n=7,2,23	-0.1 International units per liter Standard Deviation 1.77	0.5 International units per liter Standard Deviation 0.71	1.7 International units per liter Standard Deviation 5.11
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 29: AST, n=8,2,23	1.8 International units per liter Standard Deviation 7.11	1.0 International units per liter Standard Deviation 1.41	2.0 International units per liter Standard Deviation 5.42
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 43: AST, n=8,3,22	1.6 International units per liter Standard Deviation 6.74	2.0 International units per liter Standard Deviation 3.61	0.9 International units per liter Standard Deviation 4.14
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 57: AST, n=7,3,22	-0.6 International units per liter Standard Deviation 2.82	2.3 International units per liter Standard Deviation 3.06	2.0 International units per liter Standard Deviation 5.34
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 71: AST, n=8,3,21	1.9 International units per liter Standard Deviation 5.00	3.3 International units per liter Standard Deviation 4.93	-0.3 International units per liter Standard Deviation 1.98
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 85: AST, n=8,3,22	-0.8 International units per liter Standard Deviation 4.37	0.3 International units per liter Standard Deviation 2.31	-0.2 International units per liter Standard Deviation 2.20
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 113: AST, n=7,3,20	-2.7 International units per liter Standard Deviation 4.39	1.3 International units per liter Standard Deviation 4.04	-0.9 International units per liter Standard Deviation 2.50
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 155: AST, n=7,3,18	-5.0 International units per liter Standard Deviation 7.70	2.3 International units per liter Standard Deviation 0.58	-0.6 International units per liter Standard Deviation 2.66
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 197: AST, n=7,3,19	0.1 International units per liter Standard Deviation 4.91	2.7 International units per liter Standard Deviation 0.58	1.2 International units per liter Standard Deviation 3.32
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 15: LDH, n=7,2,23	4.1 International units per liter Standard Deviation 28.54	-3.5 International units per liter Standard Deviation 51.62	18.4 International units per liter Standard Deviation 32.34
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 29: LDH, n=8,2,23	-7.0 International units per liter Standard Deviation 14.95	11.0 International units per liter Standard Deviation 0.00	20.9 International units per liter Standard Deviation 22.90
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 43: LDH, n=8,3,22	12.1 International units per liter Standard Deviation 11.54	2.7 International units per liter Standard Deviation 30.62	27.2 International units per liter Standard Deviation 34.69
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 57: LDH, n=7,3,22	-5.1 International units per liter Standard Deviation 19.36	15.3 International units per liter Standard Deviation 31.02	22.4 International units per liter Standard Deviation 23.71
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 71: LDH, n=8,3,21	10.5 International units per liter Standard Deviation 29.62	13.3 International units per liter Standard Deviation 26.95	32.7 International units per liter Standard Deviation 29.90
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 85: LDH, n=8,3,22	-2.5 International units per liter Standard Deviation 26.26	3.0 International units per liter Standard Deviation 11.53	24.9 International units per liter Standard Deviation 28.66
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 113: LDH, n=7,3,20	-17.6 International units per liter Standard Deviation 17.89	6.3 International units per liter Standard Deviation 25.50	14.2 International units per liter Standard Deviation 26.43
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 155: LDH, n=7,3,17	-20.4 International units per liter Standard Deviation 32.67	1.0 International units per liter Standard Deviation 16.00	13.4 International units per liter Standard Deviation 12.63
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) Day 197: LDH, n=7,3,19	-10.9 International units per liter Standard Deviation 27.97	0.3 International units per liter Standard Deviation 20.60	16.1 International units per liter Standard Deviation 21.91

Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 15: Total bilirubin, n=7,2,23	0.571 Micromoles per liter Standard Deviation 2.2254	2.000 Micromoles per liter Standard Deviation 2.8284	-0.957 Micromoles per liter Standard Deviation 1.8944
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 29: Total bilirubin, n=8,2,23	-1.000 Micromoles per liter Standard Deviation 2.8284	-3.000 Micromoles per liter Standard Deviation 1.4142	-0.087 Micromoles per liter Standard Deviation 1.8565
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 43: Total bilirubin, n=8,3,22	-1.500 Micromoles per liter Standard Deviation 1.4142	-2.000 Micromoles per liter Standard Deviation 2.0000	-0.364 Micromoles per liter Standard Deviation 1.4653
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 57: Total bilirubin, n=7,3,22	-0.286 Micromoles per liter Standard Deviation 1.3801	-2.000 Micromoles per liter Standard Deviation 0.0000	-0.636 Micromoles per liter Standard Deviation 2.0827
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 71: Total bilirubin, n=8,3,21	0.250 Micromoles per liter Standard Deviation 1.9821	-1.333 Micromoles per liter Standard Deviation 1.1547	-0.095 Micromoles per liter Standard Deviation 2.1425
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 85: Total bilirubin, n=8,3,22	0.250 Micromoles per liter Standard Deviation 2.7124	-2.000 Micromoles per liter Standard Deviation 0.0000	-0.364 Micromoles per liter Standard Deviation 1.8138
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 113: Total bilirubin, n=7,3,20	0.000 Micromoles per liter Standard Deviation 3.2660	-1.333 Micromoles per liter Standard Deviation 1.1547	0.100 Micromoles per liter Standard Deviation 1.5183
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 155: Total bilirubin, n=7,3,18	-1.143 Micromoles per liter Standard Deviation 3.0237	-3.333 Micromoles per liter Standard Deviation 1.1547	-1.604 Micromoles per liter Standard Deviation 2.4901
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 197: Total bilirubin, n=7,3,20	0.571 Micromoles per liter Standard Deviation 2.7603	-4.000 Micromoles per liter Standard Deviation 0.0000	-1.416 Micromoles per liter Standard Deviation 1.6976
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 15: Direct bilirubin, n=7,2,23	0.0 Micromoles per liter Standard Deviation 0.00	0.0 Micromoles per liter Standard Deviation 0.00	-0.4 Micromoles per liter Standard Deviation 1.59
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 29: Direct bilirubin, n=8,2,23	-0.3 Micromoles per liter Standard Deviation 0.71	0.0 Micromoles per liter Standard Deviation 0.00	0.0 Micromoles per liter Standard Deviation 1.21
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 43: Direct bilirubin, n=8,3,22	-0.3 Micromoles per liter Standard Deviation 0.71	0.0 Micromoles per liter Standard Deviation 0.00	-0.2 Micromoles per liter Standard Deviation 1.05
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 57: Direct bilirubin, n=7,3,22	0.0 Micromoles per liter Standard Deviation 0.00	0.0 Micromoles per liter Standard Deviation 0.00	-0.4 Micromoles per liter Standard Deviation 1.18
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 71: Direct bilirubin, n=8,3,21	-0.3 Micromoles per liter Standard Deviation 0.71	0.0 Micromoles per liter Standard Deviation 0.00	-0.1 Micromoles per liter Standard Deviation 1.18
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 85: Direct bilirubin, n=8,3,22	-0.3 Micromoles per liter Standard Deviation 0.71	0.0 Micromoles per liter Standard Deviation 0.00	-0.2 Micromoles per liter Standard Deviation 1.05
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 113: Direct bilirubin, n=7,3,20	0.0 Micromoles per liter Standard Deviation 1.15	-0.7 Micromoles per liter Standard Deviation 1.15	-0.3 Micromoles per liter Standard Deviation 0.98
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 155: Direct bilirubin, n=7,3,17	-0.3 Micromoles per liter Standard Deviation 0.76	0.0 Micromoles per liter Standard Deviation 0.00	-0.2 Micromoles per liter Standard Deviation 0.97
Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin Day 197: Direct bilirubin, n=7,3,17	0.0 Micromoles per liter Standard Deviation 0.00	0.0 Micromoles per liter Standard Deviation 0.00	-0.1 Micromoles per liter Standard Deviation 1.11

Measure	Placebo n=8 Participants Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 100 mg n=3 Participants Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).	GSK2330811 300 mg n=23 Participants Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 15: Corrected calcium, n=7,2,23	0.011 Millimoles per liter Standard Deviation 0.0540	-0.020 Millimoles per liter Standard Deviation 0.0566	-0.013 Millimoles per liter Standard Deviation 0.0725
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 29: Corrected calcium, n=8,2,23	-0.035 Millimoles per liter Standard Deviation 0.0563	-0.070 Millimoles per liter Standard Deviation 0.0424	-0.036 Millimoles per liter Standard Deviation 0.0809
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 43: Corrected calcium, n=8,3,22	-0.003 Millimoles per liter Standard Deviation 0.0483	-0.060 Millimoles per liter Standard Deviation 0.0200	-0.061 Millimoles per liter Standard Deviation 0.0737
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 57: Corrected calcium, n=7,3,22	-0.003 Millimoles per liter Standard Deviation 0.0509	-0.060 Millimoles per liter Standard Deviation 0.0721	-0.069 Millimoles per liter Standard Deviation 0.0827
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 71: Corrected calcium, n=8,3,21	-0.023 Millimoles per liter Standard Deviation 0.0362	-0.020 Millimoles per liter Standard Deviation 0.0000	-0.066 Millimoles per liter Standard Deviation 0.0705
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 85: Corrected calcium, n=8,3,22	-0.043 Millimoles per liter Standard Deviation 0.0599	-0.027 Millimoles per liter Standard Deviation 0.0808	-0.049 Millimoles per liter Standard Deviation 0.0689
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 113: Corrected calcium, n=7,3,20	-0.026 Millimoles per liter Standard Deviation 0.0746	0.000 Millimoles per liter Standard Deviation 0.0346	-0.035 Millimoles per liter Standard Deviation 0.0550
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 155: Corrected calcium, n=7,3,18	-0.037 Millimoles per liter Standard Deviation 0.0678	0.000 Millimoles per liter Standard Deviation 0.0346	-0.034 Millimoles per liter Standard Deviation 0.0508
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 197: Corrected calcium, n=7,3,19	0.014 Millimoles per liter Standard Deviation 0.0862	-0.020 Millimoles per liter Standard Deviation 0.0600	-0.020 Millimoles per liter Standard Deviation 0.0629
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 15: Urea, n=7,2,23	0.0714 Millimoles per liter Standard Deviation 1.13389	-2.0000 Millimoles per liter Standard Deviation 0.00000	0.3043 Millimoles per liter Standard Deviation 1.56481
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 29: Urea, n=8,2,23	0.0000 Millimoles per liter Standard Deviation 1.13389	-0.7500 Millimoles per liter Standard Deviation 0.35355	0.3043 Millimoles per liter Standard Deviation 1.67698
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 43: Urea, n=8,3,22	0.4375 Millimoles per liter Standard Deviation 1.08356	-0.8333 Millimoles per liter Standard Deviation 0.28868	0.3182 Millimoles per liter Standard Deviation 1.34116
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 57: Urea, n=7,3,22	-0.1429 Millimoles per liter Standard Deviation 1.14434	-0.8333 Millimoles per liter Standard Deviation 0.76376	0.5682 Millimoles per liter Standard Deviation 1.30289
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 71: Urea, n=8,3,21	-0.1875 Millimoles per liter Standard Deviation 1.30760	-0.5000 Millimoles per liter Standard Deviation 0.50000	0.0952 Millimoles per liter Standard Deviation 1.50515
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 85: Urea, n=8,3,22	-0.1875 Millimoles per liter Standard Deviation 1.25178	-0.1667 Millimoles per liter Standard Deviation 0.76376	0.4091 Millimoles per liter Standard Deviation 1.40269
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 113: Urea, n=7,3,20	0.2857 Millimoles per liter Standard Deviation 1.70434	-0.8333 Millimoles per liter Standard Deviation 0.28868	0.4000 Millimoles per liter Standard Deviation 1.47434
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 155: Urea, n=7,3,18	0.2857 Millimoles per liter Standard Deviation 1.75255	-0.8333 Millimoles per liter Standard Deviation 1.15470	0.0912 Millimoles per liter Standard Deviation 1.52540
Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea Day 197: Urea, n=7,3,19	-0.0714 Millimoles per liter Standard Deviation 2.11007	-1.0000 Millimoles per liter Standard Deviation 0.50000	0.1510 Millimoles per liter Standard Deviation 1.76450