Trial Outcomes & Findings for A Study to Investigate the Efficacy and Safety of GSK3196165 in Inflammatory Hand Osteoarthritis (NCT NCT02683785)

NCT ID: NCT02683785

Last Updated: 2021-01-11

Results Overview

Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors "0" (no pain) and "10" (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score was calculated as sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value. Intent-To-Treat Population comprised of all randomized participants who received at least one dose of study treatment (GSK3196165 or placebo).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

Baseline (Day 1 Pre-dose) and Week 6

Results posted on

2021-01-11

Participant Flow

This was a multi-center, double-blind, placebo-controlled study to investigate the efficacy and safety of GSK3196165 in participants with inflammatory hand osteoarthritis. The study was conducted in five countries in Poland, United Kingdom, Netherlands, Germany and United States.

A total 121 participants were screened of which 77 were screen failures and 44 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure
Placebo
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Overall Study
STARTED
22
22
Overall Study
COMPLETED
21
18
Overall Study
NOT COMPLETED
1
4

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Overall Study
Withdrawal by Subject
1
1
Overall Study
Lost to Follow-up
0
1
Overall Study
Adverse Event
0
2

Baseline Characteristics

A Study to Investigate the Efficacy and Safety of GSK3196165 in Inflammatory Hand Osteoarthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Total
n=44 Participants
Total of all reporting groups
Age, Continuous
56.7 Years
STANDARD_DEVIATION 6.80 • n=5 Participants
60.9 Years
STANDARD_DEVIATION 6.25 • n=7 Participants
58.8 Years
STANDARD_DEVIATION 6.79 • n=5 Participants
Sex: Female, Male
Female
20 Participants
n=5 Participants
20 Participants
n=7 Participants
40 Participants
n=5 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Race/Ethnicity, Customized
White - White /Caucasian/European
22 Participants
n=5 Participants
22 Participants
n=7 Participants
44 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 Pre-dose) and Week 6

Population: Intent To Treat Population. Only non-missing data is included MMRM model.

Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors "0" (no pain) and "10" (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score was calculated as sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value. Intent-To-Treat Population comprised of all randomized participants who received at least one dose of study treatment (GSK3196165 or placebo).

Outcome measures

Outcome measures
Measure
Placebo
n=21 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=20 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Change From Baseline in 24-hour Average Hand Pain Intensity, Averaged Over the 7 Days Prior to Week 6
-1.34 Scores on scale
Standard Error 0.325
-1.70 Scores on scale
Standard Error 0.334

SECONDARY outcome

Timeframe: Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

Population: Intent To Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors "0" (no pain) and "10" (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score is calculated by sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
Week 1, n=22, 20
-0.13 Scores on scale
Standard Error 0.152
-0.59 Scores on scale
Standard Error 0.160
Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
Week 2, n=21, 20
-0.48 Scores on scale
Standard Error 0.230
-0.86 Scores on scale
Standard Error 0.239
Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
Week 3, n=21, 20
-0.74 Scores on scale
Standard Error 0.279
-1.24 Scores on scale
Standard Error 0.289
Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
Week 4, n=21, 20
-0.91 Scores on scale
Standard Error 0.291
-1.65 Scores on scale
Standard Error 0.301
Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
Week 6, n=21, 20
-1.34 Scores on scale
Standard Error 0.325
-1.70 Scores on scale
Standard Error 0.334
Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
Week 8, n=20, 19
-1.27 Scores on scale
Standard Error 0.382
-2.10 Scores on scale
Standard Error 0.393
Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
Week 10, n=20, 19
-1.18 Scores on scale
Standard Error 0.376
-2.09 Scores on scale
Standard Error 0.389
Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
Week 12, n=19, 18
-1.35 Scores on scale
Standard Error 0.402
-2.24 Scores on scale
Standard Error 0.416

SECONDARY outcome

Timeframe: Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12

Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

Participants were required to complete a daily pain NRS based on their 24-hour worst hand pain intensity with the anchors "0" (no pain) and "10" (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The score is calculated as sum of daily 24 hours worst hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
Week 6, n= 21, 20
-1.30 Scores on scale
Standard Error 0.328
-1.63 Scores on scale
Standard Error 0.337
Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
Week 1, n=22, 20
0.01 Scores on scale
Standard Error 0.174
-0.45 Scores on scale
Standard Error 0.183
Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
Week 10, n= 20, 19
-1.15 Scores on scale
Standard Error 0.394
-2.13 Scores on scale
Standard Error 0.407
Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
Week 8, n= 20, 19
-1.18 Scores on scale
Standard Error 0.394
-2.11 Scores on scale
Standard Error 0.406
Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
Week 12, n= 19, 18
-1.32 Scores on scale
Standard Error 0.415
-2.34 Scores on scale
Standard Error 0.430
Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
Week 2, n=21, 20
-0.42 Scores on scale
Standard Error 0.235
-0.69 Scores on scale
Standard Error 0.245
Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
Week 3, n=21, 20
-0.63 Scores on scale
Standard Error 0.269
-1.23 Scores on scale
Standard Error 0.278
Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
Week 4, n= 21, 20
-0.72 Scores on scale
Standard Error 0.289
-1.51 Scores on scale
Standard Error 0.299

SECONDARY outcome

Timeframe: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

Population: Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.

Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 30 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is reported.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 1
0 Percentage of participants
9 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 8
18 Percentage of participants
50 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 2
0 Percentage of participants
18 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 3
5 Percentage of participants
23 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 4
14 Percentage of participants
41 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 6
23 Percentage of participants
45 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 10
18 Percentage of participants
50 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 12
23 Percentage of participants
45 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Follow up (Week 22)
23 Percentage of participants
27 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

Population: Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.

Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 50 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 1
0 Percentage of participants
0 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 2
0 Percentage of participants
9 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 3
0 Percentage of participants
18 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 4
0 Percentage of participants
23 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 6
14 Percentage of participants
27 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 8
14 Percentage of participants
41 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 10
9 Percentage of participants
36 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Week 12
14 Percentage of participants
41 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Follow up (Week 22)
9 Percentage of participants
23 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

Population: Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.

Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 30 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 1
0 Percentage of participants
9 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 2
0 Percentage of participants
18 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 3
0 Percentage of participants
23 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 4
0 Percentage of participants
32 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 6
9 Percentage of participants
36 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 8
9 Percentage of participants
45 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 10
14 Percentage of participants
45 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 12
14 Percentage of participants
45 Percentage of participants
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Follow up (Week 22)
14 Percentage of participants
32 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)

Population: Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.

Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 50 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 1
0 Percentage of participants
0 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 2
0 Percentage of participants
5 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 3
0 Percentage of participants
14 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 4
0 Percentage of participants
18 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 6
5 Percentage of participants
18 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 8
5 Percentage of participants
32 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 10
5 Percentage of participants
27 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Week 12
9 Percentage of participants
36 Percentage of participants
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Follow up (Week 22)
5 Percentage of participants
23 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12

Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

The AUSCAN Index is a self-administered questionnaire consisting of a 15-item scale which measures pain (5 items), stiffness (1 item) and degree of disability/physical function (9 items) during the preceding 48 hours. All items are rated on NRS scale with anchors "0" (none) to "10" (extreme). The scores for the pain and physical function components were calculated as simple summation of the item scores relating to that domain, so the Pain component ranges from 0 (i.e. all pain item scores are scored 0 \[none\]) to 50 (i.e. all pain item scores are scored 10 \[extreme\]), and the Physical Function component ranges from 0 (i.e. all physical function item scores are scored 0 \[none\]) to 90 (i.e. all physical function item scores are scored 10 \[extreme\]). The total AUSCAN score was calculated as simple summation of the 15 item scores and therefore ranges from 0 to 150. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Pain, Week 1, n=22, 20
0.8 Scores on scale
Standard Error 0.98
-1.9 Scores on scale
Standard Error 1.03
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Pain, Week 2, n=21, 21
-1.8 Scores on scale
Standard Error 1.27
-3.7 Scores on scale
Standard Error 1.28
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Pain, Week 4, n=22, 21
-3.5 Scores on scale
Standard Error 1.61
-7.2 Scores on scale
Standard Error 1.64
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Pain, Week 6, n=22, 21
-6.6 Scores on scale
Standard Error 1.72
-7.6 Scores on scale
Standard Error 1.76
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Pain, Week 8, n=20, 20
-4.9 Scores on scale
Standard Error 1.93
-8.7 Scores on scale
Standard Error 1.97
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Pain, Week 10, n=20, 20
-5.3 Scores on scale
Standard Error 1.82
-10.9 Scores on scale
Standard Error 1.87
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Pain, Week 12, n=21, 19
-4.6 Scores on scale
Standard Error 1.84
-9.3 Scores on scale
Standard Error 1.91
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Stiffness, Week 1, n= 22, 20
-0.4 Scores on scale
Standard Error 0.29
-0.6 Scores on scale
Standard Error 0.31
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Stiffness, Week 2, n= 21, 21
-0.8 Scores on scale
Standard Error 0.33
-1.1 Scores on scale
Standard Error 0.33
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Stiffness, Week 4, n= 22, 21
-1.2 Scores on scale
Standard Error 0.41
-1.8 Scores on scale
Standard Error 0.42
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Stiffness, Week 6, n= 22, 21
-1.4 Scores on scale
Standard Error 0.39
-1.6 Scores on scale
Standard Error 0.40
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Stiffness, Week 8, n= 20, 20
-1.2 Scores on scale
Standard Error 0.41
-1.9 Scores on scale
Standard Error 0.42
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Stiffness, Week 10, n= 20, 20
-1.6 Scores on scale
Standard Error 0.44
-2.2 Scores on scale
Standard Error 0.45
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Stiffness, Week 12, n= 21, 19
-1.5 Scores on scale
Standard Error 0.45
-2.2 Scores on scale
Standard Error 0.47
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Physical function, Week 1, n=22, 20
-0.7 Scores on scale
Standard Error 2.08
-3.6 Scores on scale
Standard Error 2.16
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Physical function, Week 2, n=21,21
-2.8 Scores on scale
Standard Error 2.35
-5.7 Scores on scale
Standard Error 2.37
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Physical function, Week 4, n=22, 21
-6.4 Scores on scale
Standard Error 3.01
-11.3 Scores on scale
Standard Error 3.07
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Physical function, Week 6, n=22, 21
-9.1 Scores on scale
Standard Error 3.25
-11.8 Scores on scale
Standard Error 3.32
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Physical function, Week 8, n=20, 20
-8.3 Scores on scale
Standard Error 3.57
-13.2 Scores on scale
Standard Error 3.64
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Physical function, Week 10, n=20, 20
-9.0 Scores on scale
Standard Error 3.82
-15.2 Scores on scale
Standard Error 3.92
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Physical function, Week 12, n=21, 19
-7.2 Scores on scale
Standard Error 3.74
-15.4 Scores on scale
Standard Error 3.87
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Total, Week 1, n= 22, 20
-0.5 Scores on scale
Standard Error 3.07
-6.0 Scores on scale
Standard Error 3.20
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Total, Week 2, n= 21, 21
-5.7 Scores on scale
Standard Error 3.66
-10.4 Scores on scale
Standard Error 3.70
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Total, Week 4, n= 22, 21
-11.4 Scores on scale
Standard Error 4.72
-20.1 Scores on scale
Standard Error 4.83
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Total, Week 6, n= 22, 21
-17.3 Scores on scale
Standard Error 5.17
-20.7 Scores on scale
Standard Error 5.28
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Total, Week 8, n= 20, 20
-14.6 Scores on scale
Standard Error 5.70
-23.6 Scores on scale
Standard Error 5.81
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Total, Week 10, n= 20, 20
-16.1 Scores on scale
Standard Error 5.88
-28.2 Scores on scale
Standard Error 6.04
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Total, Week 12, n= 21, 19
-13.5 Scores on scale
Standard Error 5.92
-26.7 Scores on scale
Standard Error 6.12

SECONDARY outcome

Timeframe: Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12

Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

Swollen Hand Joint Count was measured by the total number of soft tissue swollen hand joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joint across both hands. In case of missing observations for soft tissue swollen hand joints then the remaining observations were assessed and weighted by dividing the number presented by the number of non-missing, and by multiplying by 30 for the joint count. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit
Week 8, n = 20, 20
-3.0 Swollen joints
Standard Error 0.92
-2.8 Swollen joints
Standard Error 0.94
Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit
Week 12, n = 21, 19
-2.9 Swollen joints
Standard Error 0.91
-3.1 Swollen joints
Standard Error 0.93
Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit
Week 1, n = 22, 21
-0.3 Swollen joints
Standard Error 0.64
-0.3 Swollen joints
Standard Error 0.66
Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit
Week 2, n = 21, 21
-1.6 Swollen joints
Standard Error 0.85
-1.2 Swollen joints
Standard Error 0.86
Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit
Week 4, n = 22, 21
-1.6 Swollen joints
Standard Error 0.76
-2.1 Swollen joints
Standard Error 0.78
Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit
Week 6, n = 22, 21
-3.7 Swollen joints
Standard Error 0.83
-2.3 Swollen joints
Standard Error 0.85
Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit
Week 10, n = 20, 20
-2.6 Swollen joints
Standard Error 1.08
-2.9 Swollen joints
Standard Error 1.10

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 4, 6, 8, 10, and 12

Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data was included in the MMRM model.

Tender Hand Joint Count was measured by the total number of tender joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joints across both hands. A joint was considered tender if it was scored \>0 on the tender joint severity scale. Joints were rated 0=no pain/tenderness, 1=mild pain, 2=moderate pain and 3=severe pain. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Change From Baseline in Number of Tender Hand Joints at Each Visit
Week 1, n= 22, 21
-0.6 Scores on scale
Standard Error 1.10
-1.8 Scores on scale
Standard Error 1.13
Change From Baseline in Number of Tender Hand Joints at Each Visit
Week 2, n= 21, 21
-1.7 Scores on scale
Standard Error 1.15
-2.1 Scores on scale
Standard Error 1.17
Change From Baseline in Number of Tender Hand Joints at Each Visit
Week 8, n= 20, 20
-2.4 Scores on scale
Standard Error 1.36
-3.9 Scores on scale
Standard Error 1.39
Change From Baseline in Number of Tender Hand Joints at Each Visit
Week 12, n= 21, 19
-3.5 Scores on scale
Standard Error 1.46
-4.0 Scores on scale
Standard Error 1.51
Change From Baseline in Number of Tender Hand Joints at Each Visit
Week 4, n= 22, 21
-1.1 Scores on scale
Standard Error 1.33
-3.0 Scores on scale
Standard Error 1.36
Change From Baseline in Number of Tender Hand Joints at Each Visit
Week 6, n= 22, 21
-3.7 Scores on scale
Standard Error 1.27
-4.2 Scores on scale
Standard Error 1.30
Change From Baseline in Number of Tender Hand Joints at Each Visit
Week 10, n= 20, 20
-3.7 Scores on scale
Standard Error 1.45
-4.4 Scores on scale
Standard Error 1.48

SECONDARY outcome

Timeframe: Baseline (Day 1 Pre-dose), Weeks 2, 4, 8, and 12

Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

Physicians were required to complete the global assessment of disease activity using single PhGA item with a NRS ranging from 0 (none) to 10 (extremely active). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity
Week 2, n= 19, 14
-1.8 Scores on scale
Standard Error 0.39
-1.5 Scores on scale
Standard Error 0.45
Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity
Week 4, n= 20, 15
-2.1 Scores on scale
Standard Error 0.44
-2.6 Scores on scale
Standard Error 0.50
Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity
Week 12, n= 18, 14
-2.7 Scores on scale
Standard Error 0.56
-3.0 Scores on scale
Standard Error 0.63
Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity
Week 8, n= 17, 15
-2.2 Scores on scale
Standard Error 0.52
-3.4 Scores on scale
Standard Error 0.57

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, and 12

Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.

Participants were required to complete the global assessment of disease activity using single PtGA item with an NRS ranging from 0 (very well) to 10 (very poor). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity
Week 2, n= 20, 21
-0.4 Scores on scale
Standard Error 0.36
-0.6 Scores on scale
Standard Error 0.35
Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity
Week 4, n= 21, 21
-0.6 Scores on scale
Standard Error 0.42
-1.3 Scores on scale
Standard Error 0.42
Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity
Week 8, n= 19, 20
-0.9 Scores on scale
Standard Error 0.47
-1.8 Scores on scale
Standard Error 0.46
Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity
Week 12, n= 20, 19
-0.7 Scores on scale
Standard Error 0.46
-1.8 Scores on scale
Standard Error 0.46

SECONDARY outcome

Timeframe: Up to Week 22

Population: Safety Population

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who received at least one dose of study treatment (GSK3196165 or placebo) were included in Safety Population.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Any AE
11 Participants
13 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Any SAE
1 Participants
2 Participants

SECONDARY outcome

Timeframe: Up to Week 22

Population: Safety Population

Adverse events of special interest (AESI) included serious infections like serious respiratory infections and tuberculosis and other opportunistic infections. Number of participants with infections has been reported.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Number of Participants With Infections
Serious Infections
0 Participants
0 Participants
Number of Participants With Infections
Opportunistic Infections
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Up to Week 22

Population: Safety Population

Pulmonary events like pulmonary alveolar proteinosis (PAP), persistent (for 3 consecutive weeks) reduction in diffusing capacity of the lungs for carbon monoxide (DLCO) \> 15 percentage, persistent (for 3 consecutive weeks) cough and/or dyspnea and non- life threatening pulmonary changes related to surfactant accumulation is presented.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Number of Participants With Pulmonary Events
Persistent Cough
0 Participants
0 Participants
Number of Participants With Pulmonary Events
Abnormal Lung Auscultation
0 Participants
0 Participants
Number of Participants With Pulmonary Events
Persistent dyspnea
0 Participants
0 Participants
Number of Participants With Pulmonary Events
Persistent decrease in DLCO
0 Participants
0 Participants
Number of Participants With Pulmonary Events
PAP
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Up to Week 22

Population: Intent-to-Treat Population. Only those participants with data available post-Baseline are reported.

Serum samples were collected at indicated time points for anti-drug antibody (ADA) measurements. Anti-GSK3196165 binding antibody detection assay using tiered testing schema: screening, confirmation and titration steps was used for immunogenicity analysis. Samples taken after dosing with GSK3196165 that have a value at or above the cut-point were considered treatment-emergent ADA-positive. The number of participants with change from Baseline to any time post Baseline in the results of immunogenicity assessment as indicated by: negative to positive, positive to positive, positive to negative and negative to negative are presented.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 Participants
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Number of Participants With Anti-GSK3196165 Binding Antibodies
Negative to positive
0 Participants
1 Participants
Number of Participants With Anti-GSK3196165 Binding Antibodies
Positive to negative
0 Participants
0 Participants
Number of Participants With Anti-GSK3196165 Binding Antibodies
Positive to positive
0 Participants
0 Participants
Number of Participants With Anti-GSK3196165 Binding Antibodies
Negative to negative
22 Participants
20 Participants

SECONDARY outcome

Timeframe: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22

Population: PK Population

Blood samples were collected at indicated time points and CL/F was estimated using population PK analysis. Participants in the 'Safety' population who have at least one valid PK assessment were included Pharmacokinetic (PK) Population.

Outcome measures

Outcome measures
Measure
Placebo
n=21 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Apparent Clearance After Subcutaneous Administration (CL/F) of GSK3196165
4.94 Liters per day
Geometric Coefficient of Variation 68.8

SECONDARY outcome

Timeframe: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22

Population: PK Population.

Blood samples were collected at indicated time points and Vss/F was estimated using population PK analysis.

Outcome measures

Outcome measures
Measure
Placebo
n=21 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Apparent Steady State Volume of Distribution After Subcutaneous Administration (Vss/F) of GSK3196165
36.5 Liters
Geometric Coefficient of Variation 61.5

SECONDARY outcome

Timeframe: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22

Population: PK Population

Blood samples were collected at indicated time points and Ka was estimated using population PK analysis.

Outcome measures

Outcome measures
Measure
Placebo
n=21 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Absoption Rate Constant (Ka) of GSK3196165
0.205 Per day
Geometric Coefficient of Variation 72.3

SECONDARY outcome

Timeframe: Pre-dose on Day 3, Weeks 1, 4, 6, 12, follow up (Week 22)

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

Blood samples were collected at indicated time points for pharmacokinetic analysis.

Outcome measures

Outcome measures
Measure
Placebo
n=22 Participants
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Serum Concentration of GSK3196165 by Visit
Day 3, n= 18
2457.05 Nanogram per milliliter
Geometric Coefficient of Variation 94.74
Serum Concentration of GSK3196165 by Visit
Week 1, n= 21
1767.55 Nanogram per milliliter
Geometric Coefficient of Variation 46.96
Serum Concentration of GSK3196165 by Visit
Week 4, n= 21
2821.12 Nanogram per milliliter
Geometric Coefficient of Variation 61.00
Serum Concentration of GSK3196165 by Visit
Week 6, n= 20
1802.09 Nanogram per milliliter
Geometric Coefficient of Variation 60.42
Serum Concentration of GSK3196165 by Visit
Week 12, n= 8
800.96 Nanogram per milliliter
Geometric Coefficient of Variation 176.33
Serum Concentration of GSK3196165 by Visit
Follow up (Week 22), n= 12
56.40 Nanogram per milliliter
Geometric Coefficient of Variation 346.41

Adverse Events

Placebo

Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths

GSK3196165 180mg

Serious events: 2 serious events
Other events: 10 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=22 participants at risk
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 participants at risk
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Cardiac disorders
ATRIAL FIBRILLATION
4.5%
1/22 • Number of events 1 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
0.00%
0/22 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
Injury, poisoning and procedural complications
HUMERUS FRACTURE
0.00%
0/22 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
4.5%
1/22 • Number of events 1 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
Vascular disorders
HYPERTENSIVE CRISIS
0.00%
0/22 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
4.5%
1/22 • Number of events 1 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.

Other adverse events

Other adverse events
Measure
Placebo
n=22 participants at risk
Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
GSK3196165 180mg
n=22 participants at risk
Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71).
Cardiac disorders
PALPITATIONS
9.1%
2/22 • Number of events 2 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
0.00%
0/22 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
General disorders
INJECTION SITE ERYTHEMA
0.00%
0/22 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
9.1%
2/22 • Number of events 3 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
General disorders
INJECTION SITE RASH
0.00%
0/22 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
9.1%
2/22 • Number of events 6 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
Infections and infestations
CONJUNCTIVITIS
0.00%
0/22 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
9.1%
2/22 • Number of events 2 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
Infections and infestations
HERPES ZOSTER
0.00%
0/22 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
9.1%
2/22 • Number of events 2 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
Infections and infestations
NASOPHARYNGITIS
4.5%
1/22 • Number of events 1 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
9.1%
2/22 • Number of events 3 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
Infections and infestations
URINARY TRACT INFECTION
0.00%
0/22 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
9.1%
2/22 • Number of events 2 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
Respiratory, thoracic and mediastinal disorders
COUGH
9.1%
2/22 • Number of events 3 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.
9.1%
2/22 • Number of events 2 • Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Non-serious AEs and SAE for Safety Population was reported.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

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