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

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ClinicalTrials.gov Identifier: NCT02683785
Recruitment Status : Completed
First Posted : February 17, 2016
Results First Posted : December 14, 2018
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Osteoarthritis
Interventions Drug: GSK3196165
Drug: Placebo
Enrollment 44
Recruitment Details 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.
Pre-assignment Details A total 121 participants were screened of which 77 were screen failures and 44 participants were enrolled in the study.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description 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). 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).
Period Title: Overall Study
Started 22 22
Completed 21 18
Not Completed 1 4
Reason Not Completed
Withdrawal by Subject             1             1
Lost to Follow-up             0             1
Adverse Event             0             2
Arm/Group Title Placebo GSK3196165 180mg Total
Hide Arm/Group Description 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). 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 of all reporting groups
Overall Number of Baseline Participants 22 22 44
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 22 participants 44 participants
56.7  (6.80) 60.9  (6.25) 58.8  (6.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 22 participants 44 participants
Female
20
  90.9%
20
  90.9%
40
  90.9%
Male
2
   9.1%
2
   9.1%
4
   9.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
White - White /Caucasian/European Number Analyzed 22 participants 22 participants 44 participants
22 22 44
1.Primary Outcome
Title Change From Baseline in 24-hour Average Hand Pain Intensity, Averaged Over the 7 Days Prior to Week 6
Hide Description 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).
Time Frame Baseline (Day 1 Pre-dose) and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent To Treat Population. Only non-missing data is included MMRM model.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 21 20
Least Squares Mean (Standard Error)
Unit of Measure: Scores on scale
-1.34  (0.325) -1.70  (0.334)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.442
Comments MMRM model with fixed effects of Baseline Value,Treatment Group,Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used.p-value corresponds to the difference over placebo measure and confidence interval
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-1.31 to 0.58
Estimation Comments Difference from placebo for Week 6 is presented.
2.Secondary Outcome
Title Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
Hide Description 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.
Time Frame Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Least Squares Mean (Standard Error)
Unit of Measure: Scores on scale
Week 1, n=22, 20 Number Analyzed 22 participants 20 participants
-0.13  (0.152) -0.59  (0.160)
Week 2, n=21, 20 Number Analyzed 21 participants 20 participants
-0.48  (0.230) -0.86  (0.239)
Week 3, n=21, 20 Number Analyzed 21 participants 20 participants
-0.74  (0.279) -1.24  (0.289)
Week 4, n=21, 20 Number Analyzed 21 participants 20 participants
-0.91  (0.291) -1.65  (0.301)
Week 6, n=21, 20 Number Analyzed 21 participants 20 participants
-1.34  (0.325) -1.70  (0.334)
Week 8, n=20, 19 Number Analyzed 20 participants 19 participants
-1.27  (0.382) -2.10  (0.393)
Week 10, n=20, 19 Number Analyzed 20 participants 19 participants
-1.18  (0.376) -2.09  (0.389)
Week 12, n=19, 18 Number Analyzed 19 participants 18 participants
-1.35  (0.402) -2.24  (0.416)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-0.90 to -0.01
Estimation Comments Difference from placebo for Week 1 is presented
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.257
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-1.05 to 0.29
Estimation Comments Difference from placebo for Week 2 is presented
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.220
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-1.31 to 0.31
Estimation Comments Difference from placebo for Week 3 is presented
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.085
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.74
Confidence Interval (2-Sided) 95%
-1.59 to 0.11
Estimation Comments Difference from placebo for Week 4 is presented
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.442
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-1.31 to 0.58
Estimation Comments Difference from placebo for Week 6 is presented
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.139
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.83
Confidence Interval (2-Sided) 95%
-1.93 to 0.28
Estimation Comments Difference from placebo for Week 8 is presented
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.103
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.90
Confidence Interval (2-Sided) 95%
-2.00 to 0.19
Estimation Comments Difference from placebo for Week 10 is presented
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.132
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.89
Confidence Interval (2-Sided) 95%
-2.06 to 0.28
Estimation Comments Difference from placebo for Week 12 is presented.
3.Secondary Outcome
Title Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
Hide Description 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.
Time Frame Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Least Squares Mean (Standard Error)
Unit of Measure: Scores on scale
Week 1, n=22, 20 Number Analyzed 22 participants 20 participants
0.01  (0.174) -0.45  (0.183)
Week 2, n=21, 20 Number Analyzed 21 participants 20 participants
-0.42  (0.235) -0.69  (0.245)
Week 3, n=21, 20 Number Analyzed 21 participants 20 participants
-0.63  (0.269) -1.23  (0.278)
Week 4, n= 21, 20 Number Analyzed 21 participants 20 participants
-0.72  (0.289) -1.51  (0.299)
Week 6, n= 21, 20 Number Analyzed 21 participants 20 participants
-1.30  (0.328) -1.63  (0.337)
Week 8, n= 20, 19 Number Analyzed 20 participants 19 participants
-1.18  (0.394) -2.11  (0.406)
Week 10, n= 20, 19 Number Analyzed 20 participants 19 participants
-1.15  (0.394) -2.13  (0.407)
Week 12, n= 19, 18 Number Analyzed 19 participants 18 participants
-1.32  (0.415) -2.34  (0.430)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.082
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.97 to 0.06
Estimation Comments Difference from placebo for Week 1 is presented.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.426
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.96 to 0.41
Estimation Comments Difference from placebo for Week 2 is presented
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.129
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.60
Confidence Interval (2-Sided) 95%
-1.38 to 0.18
Estimation Comments Difference from placebo for Week 3 is presented
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.067
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.78
Confidence Interval (2-Sided) 95%
-1.63 to 0.06
Estimation Comments Difference from placebo for Week 4 is presented.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.494
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-1.28 to 0.63
Estimation Comments Difference from placebo for Week 6 is presented
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.107
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.94
Confidence Interval (2-Sided) 95%
-2.08 to 0.21
Estimation Comments Difference from placebo for Week 8 is presented.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.092
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.98
Confidence Interval (2-Sided) 95%
-2.13 to 0.17
Estimation Comments Difference from placebo for Week 10 is presented.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.098
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.01
Confidence Interval (2-Sided) 95%
-2.22 to 0.20
Estimation Comments Difference from placebo for Week 12 is presented.
4.Secondary Outcome
Title Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Hide Description 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.
Time Frame Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Measure Type: Number
Unit of Measure: Percentage of participants
Week 1 0 9
Week 2 0 18
Week 3 5 23
Week 4 14 41
Week 6 23 45
Week 8 18 50
Week 10 18 50
Week 12 23 45
Follow up (Week 22) 23 27
5.Secondary Outcome
Title Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Hide Description 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.
Time Frame Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Measure Type: Number
Unit of Measure: Percentage of participants
Week 1 0 0
Week 2 0 9
Week 3 0 18
Week 4 0 23
Week 6 14 27
Week 8 14 41
Week 10 9 36
Week 12 14 41
Follow up (Week 22) 9 23
6.Secondary Outcome
Title Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Hide Description 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.
Time Frame Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Measure Type: Number
Unit of Measure: Percentage of participants
Week 1 0 9
Week 2 0 18
Week 3 0 23
Week 4 0 32
Week 6 9 36
Week 8 9 45
Week 10 14 45
Week 12 14 45
Follow up (Week 22) 14 32
7.Secondary Outcome
Title Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Hide Description 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.
Time Frame Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Measure Type: Number
Unit of Measure: Percentage of participants
Week 1 0 0
Week 2 0 5
Week 3 0 14
Week 4 0 18
Week 6 5 18
Week 8 5 32
Week 10 5 27
Week 12 9 36
Follow up (Week 22) 5 23
8.Secondary Outcome
Title Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
Hide Description 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.
Time Frame Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Least Squares Mean (Standard Error)
Unit of Measure: Scores on scale
Pain, Week 1, n=22, 20 Number Analyzed 22 participants 20 participants
0.8  (0.98) -1.9  (1.03)
Pain, Week 2, n=21, 21 Number Analyzed 21 participants 21 participants
-1.8  (1.27) -3.7  (1.28)
Pain, Week 4, n=22, 21 Number Analyzed 22 participants 21 participants
-3.5  (1.61) -7.2  (1.64)
Pain, Week 6, n=22, 21 Number Analyzed 22 participants 21 participants
-6.6  (1.72) -7.6  (1.76)
Pain, Week 8, n=20, 20 Number Analyzed 20 participants 20 participants
-4.9  (1.93) -8.7  (1.97)
Pain, Week 10, n=20, 20 Number Analyzed 20 participants 20 participants
-5.3  (1.82) -10.9  (1.87)
Pain, Week 12, n=21, 19 Number Analyzed 21 participants 19 participants
-4.6  (1.84) -9.3  (1.91)
Stiffness, Week 1, n= 22, 20 Number Analyzed 22 participants 20 participants
-0.4  (0.29) -0.6  (0.31)
Stiffness, Week 2, n= 21, 21 Number Analyzed 21 participants 21 participants
-0.8  (0.33) -1.1  (0.33)
Stiffness, Week 4, n= 22, 21 Number Analyzed 22 participants 21 participants
-1.2  (0.41) -1.8  (0.42)
Stiffness, Week 6, n= 22, 21 Number Analyzed 22 participants 21 participants
-1.4  (0.39) -1.6  (0.40)
Stiffness, Week 8, n= 20, 20 Number Analyzed 20 participants 20 participants
-1.2  (0.41) -1.9  (0.42)
Stiffness, Week 10, n= 20, 20 Number Analyzed 20 participants 20 participants
-1.6  (0.44) -2.2  (0.45)
Stiffness, Week 12, n= 21, 19 Number Analyzed 21 participants 19 participants
-1.5  (0.45) -2.2  (0.47)
Physical function, Week 1, n=22, 20 Number Analyzed 22 participants 20 participants
-0.7  (2.08) -3.6  (2.16)
Physical function, Week 2, n=21,21 Number Analyzed 21 participants 21 participants
-2.8  (2.35) -5.7  (2.37)
Physical function, Week 4, n=22, 21 Number Analyzed 22 participants 21 participants
-6.4  (3.01) -11.3  (3.07)
Physical function, Week 6, n=22, 21 Number Analyzed 22 participants 21 participants
-9.1  (3.25) -11.8  (3.32)
Physical function, Week 8, n=20, 20 Number Analyzed 20 participants 20 participants
-8.3  (3.57) -13.2  (3.64)
Physical function, Week 10, n=20, 20 Number Analyzed 20 participants 20 participants
-9.0  (3.82) -15.2  (3.92)
Physical function, Week 12, n=21, 19 Number Analyzed 21 participants 19 participants
-7.2  (3.74) -15.4  (3.87)
Total, Week 1, n= 22, 20 Number Analyzed 22 participants 20 participants
-0.5  (3.07) -6.0  (3.20)
Total, Week 2, n= 21, 21 Number Analyzed 21 participants 21 participants
-5.7  (3.66) -10.4  (3.70)
Total, Week 4, n= 22, 21 Number Analyzed 22 participants 21 participants
-11.4  (4.72) -20.1  (4.83)
Total, Week 6, n= 22, 21 Number Analyzed 22 participants 21 participants
-17.3  (5.17) -20.7  (5.28)
Total, Week 8, n= 20, 20 Number Analyzed 20 participants 20 participants
-14.6  (5.70) -23.6  (5.81)
Total, Week 10, n= 20, 20 Number Analyzed 20 participants 20 participants
-16.1  (5.88) -28.2  (6.04)
Total, Week 12, n= 21, 19 Number Analyzed 21 participants 19 participants
-13.5  (5.92) -26.7  (6.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.061
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-5.6 to 0.1
Estimation Comments For Pain component, Week 1
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.282
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-5.6 to 1.7
Estimation Comments For Pain component, Week 2
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.113
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.7
Confidence Interval (2-Sided) 95%
-8.4 to 0.9
Estimation Comments For Pain component Week 4
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.695
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-5.9 to 4.0
Estimation Comments For Pain component, Week 6
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.176
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.8
Confidence Interval (2-Sided) 95%
-9.4 to 1.8
Estimation Comments For Pain component, Week 8
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.041
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.5
Confidence Interval (2-Sided) 95%
-10.8 to -0.2
Estimation Comments For Pain component, Week 10
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.082
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.7
Confidence Interval (2-Sided) 95%
-10.1 to 0.6
Estimation Comments For Pain component, Week 12
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.587
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.1 to 0.6
Estimation Comments For Stiffness component, Week 1
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.457
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.3 to 0.6
Estimation Comments For Stiffness component, Week 2
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.298
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.8 to 0.6
Estimation Comments For Stiffness component, Week 4
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.726
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.3 to 0.9
Estimation Comments For Stiffness component, Week 6
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.213
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.9 to 0.4
Estimation Comments For Stiffness component, Week 8
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.331
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.9 to 0.7
Estimation Comments For Stiffness component, Week 10
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.248
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.1 to 0.6
Estimation Comments For Stiffness component, Week 12
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.350
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.9
Confidence Interval (2-Sided) 95%
-9.0 to 3.3
Estimation Comments For Physical Function component, Week 1
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.383
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.0
Confidence Interval (2-Sided) 95%
-9.8 to 3.8
Estimation Comments For Physical Function component, Week 2
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.271
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-13.5 to 3.9
Estimation Comments For Physical Function component, Week 4
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.565
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.7
Confidence Interval (2-Sided) 95%
-12.1 to 6.7
Estimation Comments For Physical Function component, Week 6
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.343
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.9
Confidence Interval (2-Sided) 95%
-15.2 to 5.4
Estimation Comments For Physical Function component, Week 8
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.266
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -6.2
Confidence Interval (2-Sided) 95%
-17.3 to 4.9
Estimation Comments For Physical Function component, Week 10
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.136
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -8.2
Confidence Interval (2-Sided) 95%
-19.1 to 2.7
Estimation Comments For Physical Function component, Week 12
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.230
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.5
Confidence Interval (2-Sided) 95%
-14.5 to 3.6
Estimation Comments For Total of all component scores, Week 1
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.381
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.6
Confidence Interval (2-Sided) 95%
-15.2 to 5.9
Estimation Comments For Total of all component scores, Week 2
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.207
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -8.7
Confidence Interval (2-Sided) 95%
-22.4 to 5.0
Estimation Comments For Total of all component scores, Week 4
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.648
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.4
Confidence Interval (2-Sided) 95%
-18.4 to 11.6
Estimation Comments For Total of all component scores, Week 6
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.278
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -9.0
Confidence Interval (2-Sided) 95%
-25.4 to 7.5
Estimation Comments For Total of all component scores, Week 8
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.160
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -12.1
Confidence Interval (2-Sided) 95%
-29.1 to 5.0
Estimation Comments For Total of all component scores, Week 10
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.127
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -13.3
Confidence Interval (2-Sided) 95%
-30.5 to 3.9
Estimation Comments For Total of all component scores, Week 12
9.Secondary Outcome
Title Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit
Hide Description 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.
Time Frame Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Least Squares Mean (Standard Error)
Unit of Measure: Swollen joints
Week 1, n = 22, 21 Number Analyzed 22 participants 21 participants
-0.3  (0.64) -0.3  (0.66)
Week 2, n = 21, 21 Number Analyzed 21 participants 21 participants
-1.6  (0.85) -1.2  (0.86)
Week 4, n = 22, 21 Number Analyzed 22 participants 21 participants
-1.6  (0.76) -2.1  (0.78)
Week 6, n = 22, 21 Number Analyzed 22 participants 21 participants
-3.7  (0.83) -2.3  (0.85)
Week 8, n = 20, 20 Number Analyzed 20 participants 20 participants
-3.0  (0.92) -2.8  (0.94)
Week 10, n = 20, 20 Number Analyzed 20 participants 20 participants
-2.6  (1.08) -2.9  (1.10)
Week 12, n = 21, 19 Number Analyzed 21 participants 19 participants
-2.9  (0.91) -3.1  (0.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.957
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.9 to 1.8
Estimation Comments Difference from placebo for Week 1 is presented
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.775
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-2.1 to 2.8
Estimation Comments Difference from placebo for Week 2 is presented
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.624
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-2.7 to 1.7
Estimation Comments Difference from placebo for Week 4 is presented
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.243
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-1.0 to 3.8
Estimation Comments Difference from placebo for Week 6 is presented
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.875
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-2.5 to 2.9
Estimation Comments Difference from placebo for Week 8 is presented
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.848
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-3.4 to 2.8
Estimation Comments Difference from placebo for Week 10 is presented
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.883
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-2.8 to 2.4
Estimation Comments Difference from placebo for Week 12 is presented
10.Secondary Outcome
Title Change From Baseline in Number of Tender Hand Joints at Each Visit
Hide Description 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.
Time Frame Baseline, Weeks 1, 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Least Squares Mean (Standard Error)
Unit of Measure: Scores on scale
Week 1, n= 22, 21 Number Analyzed 22 participants 21 participants
-0.6  (1.10) -1.8  (1.13)
Week 2, n= 21, 21 Number Analyzed 21 participants 21 participants
-1.7  (1.15) -2.1  (1.17)
Week 4, n= 22, 21 Number Analyzed 22 participants 21 participants
-1.1  (1.33) -3.0  (1.36)
Week 6, n= 22, 21 Number Analyzed 22 participants 21 participants
-3.7  (1.27) -4.2  (1.30)
Week 8, n= 20, 20 Number Analyzed 20 participants 20 participants
-2.4  (1.36) -3.9  (1.39)
Week 10, n= 20, 20 Number Analyzed 20 participants 20 participants
-3.7  (1.45) -4.4  (1.48)
Week 12, n= 21, 19 Number Analyzed 21 participants 19 participants
-3.5  (1.46) -4.0  (1.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.463
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-4.4 to 2.0
Estimation Comments Difference from placebo for Week 1 is presented
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.809
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-3.7 to 2.9
Estimation Comments Difference from placebo for Week 2 is presented
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.324
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-5.8 to 2.0
Estimation Comments Difference from placebo for Week 4 is presented
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.783
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-4.2 to 3.2
Estimation Comments Difference from placebo for Week 6 is presented
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.464
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-5.4 to 2.5
Estimation Comments Difference from placebo for Week 8 is presented
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.736
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-4.9 to 3.5
Estimation Comments Difference from placebo for Week 10 is presented
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.806
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-4.8 to 3.7
Estimation Comments Difference from placebo for Week 12 is presented
11.Secondary Outcome
Title Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity
Hide Description 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.
Time Frame Baseline (Day 1 Pre-dose), Weeks 2, 4, 8, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Least Squares Mean (Standard Error)
Unit of Measure: Scores on scale
Week 2, n= 19, 14 Number Analyzed 19 participants 14 participants
-1.8  (0.39) -1.5  (0.45)
Week 4, n= 20, 15 Number Analyzed 20 participants 15 participants
-2.1  (0.44) -2.6  (0.50)
Week 8, n= 17, 15 Number Analyzed 17 participants 15 participants
-2.2  (0.52) -3.4  (0.57)
Week 12, n= 18, 14 Number Analyzed 18 participants 14 participants
-2.7  (0.56) -3.0  (0.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.586
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.9 to 1.6
Estimation Comments Difference from placebo for Week 2 is presented
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.416
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.9 to 0.8
Estimation Comments Difference from placebo for Week 4 is presented
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.120
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-2.8 to 0.3
Estimation Comments Difference from placebo for Week 8 is presented
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.687
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-2.1 to 1.4
Estimation Comments Difference from placebo for Week 12 is presented
12.Secondary Outcome
Title Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity
Hide Description 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.
Time Frame Baseline, Weeks 2, 4, 8, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Least Squares Mean (Standard Error)
Unit of Measure: Scores on scale
Week 2, n= 20, 21 Number Analyzed 20 participants 21 participants
-0.4  (0.36) -0.6  (0.35)
Week 4, n= 21, 21 Number Analyzed 21 participants 21 participants
-0.6  (0.42) -1.3  (0.42)
Week 8, n= 19, 20 Number Analyzed 19 participants 20 participants
-0.9  (0.47) -1.8  (0.46)
Week 12, n= 20, 19 Number Analyzed 20 participants 19 participants
-0.7  (0.46) -1.8  (0.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.651
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.3 to 0.8
Estimation Comments Difference from placebo for Week 2 is presented.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.271
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.9 to 0.5
Estimation Comments Difference from placebo for Week 4 is presented
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.186
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.2 to 0.4
Estimation Comments Difference from placebo for Week 8 is presented
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK3196165 180mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments MMRM model with fixed effects of Baseline Value, Treatment Group, Visit and Treatment Group by Visit Interaction was used. Unstructured covariance structure was used. p-value corresponds to the difference over placebo measure and confidence interval.
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.4 to 0.2
Estimation Comments Difference from placebo for Week 12 is presented
13.Secondary Outcome
Title Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Hide Description 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.
Time Frame Up to Week 22
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
11
  50.0%
13
  59.1%
Any SAE
1
   4.5%
2
   9.1%
14.Secondary Outcome
Title Number of Participants With Infections
Hide Description 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.
Time Frame Up to Week 22
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Measure Type: Count of Participants
Unit of Measure: Participants
Serious Infections
0
   0.0%
0
   0.0%
Opportunistic Infections
0
   0.0%
0
   0.0%
15.Secondary Outcome
Title Number of Participants With Pulmonary Events
Hide Description 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.
Time Frame Up to Week 22
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Measure Type: Count of Participants
Unit of Measure: Participants
Persistent dyspnea
0
   0.0%
0
   0.0%
Persistent decrease in DLCO
0
   0.0%
0
   0.0%
Persistent Cough
0
   0.0%
0
   0.0%
Abnormal Lung Auscultation
0
   0.0%
0
   0.0%
PAP
0
   0.0%
0
   0.0%
16.Secondary Outcome
Title Number of Participants With Anti-GSK3196165 Binding Antibodies
Hide Description 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.
Time Frame Up to Week 22
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with data available post-Baseline are reported.
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 22 22
Measure Type: Count of Participants
Unit of Measure: Participants
Negative to positive
0
   0.0%
1
   4.5%
Positive to positive
0
   0.0%
0
   0.0%
Positive to negative
0
   0.0%
0
   0.0%
Negative to negative
22
 100.0%
20
  90.9%
17.Secondary Outcome
Title Apparent Clearance After Subcutaneous Administration (CL/F) of GSK3196165
Hide Description 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.
Time Frame Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title GSK3196165 180mg
Hide Arm/Group Description:
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 Number of Participants Analyzed 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters per day
4.94
(68.8%)
18.Secondary Outcome
Title Apparent Steady State Volume of Distribution After Subcutaneous Administration (Vss/F) of GSK3196165
Hide Description Blood samples were collected at indicated time points and Vss/F was estimated using population PK analysis.
Time Frame Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population.
Arm/Group Title GSK3196165 180mg
Hide Arm/Group Description:
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 Number of Participants Analyzed 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters
36.5
(61.5%)
19.Secondary Outcome
Title Absoption Rate Constant (Ka) of GSK3196165
Hide Description Blood samples were collected at indicated time points and Ka was estimated using population PK analysis.
Time Frame Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title GSK3196165 180mg
Hide Arm/Group Description:
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 Number of Participants Analyzed 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Per day
0.205
(72.3%)
20.Secondary Outcome
Title Serum Concentration of GSK3196165 by Visit
Hide Description Blood samples were collected at indicated time points for pharmacokinetic analysis.
Time Frame Pre-dose on Day 3, Weeks 1, 4, 6, 12, follow up (Week 22)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK3196165 180 mg
Hide Arm/Group Description:
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 Number of Participants Analyzed 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram per milliliter
Day 3, n= 18 Number Analyzed 18 participants
2457.05
(94.74%)
Week 1, n= 21 Number Analyzed 21 participants
1767.55
(46.96%)
Week 4, n= 21 Number Analyzed 21 participants
2821.12
(61.00%)
Week 6, n= 20 Number Analyzed 20 participants
1802.09
(60.42%)
Week 12, n= 8 Number Analyzed 8 participants
800.96
(176.33%)
Follow up (Week 22), n= 12 Number Analyzed 12 participants
56.40
(346.41%)
Time Frame Non-serious adverse events (AEs) and serious AEs were collected up to Week 22.
Adverse Event Reporting Description Non-serious AEs and SAE for Safety Population was reported.
 
Arm/Group Title Placebo GSK3196165 180mg
Hide Arm/Group Description 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). 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).
All-Cause Mortality
Placebo GSK3196165 180mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)      0/22 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo GSK3196165 180mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/22 (4.55%)      2/22 (9.09%)    
Cardiac disorders     
ATRIAL FIBRILLATION  1  1/22 (4.55%)  1 0/22 (0.00%)  0
Injury, poisoning and procedural complications     
HUMERUS FRACTURE  1  0/22 (0.00%)  0 1/22 (4.55%)  1
Vascular disorders     
HYPERTENSIVE CRISIS  1  0/22 (0.00%)  0 1/22 (4.55%)  1
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo GSK3196165 180mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/22 (18.18%)      10/22 (45.45%)    
Cardiac disorders     
PALPITATIONS  1  2/22 (9.09%)  2 0/22 (0.00%)  0
General disorders     
INJECTION SITE ERYTHEMA  1  0/22 (0.00%)  0 2/22 (9.09%)  3
INJECTION SITE RASH  1  0/22 (0.00%)  0 2/22 (9.09%)  6
Infections and infestations     
CONJUNCTIVITIS  1  0/22 (0.00%)  0 2/22 (9.09%)  2
HERPES ZOSTER  1  0/22 (0.00%)  0 2/22 (9.09%)  2
NASOPHARYNGITIS  1  1/22 (4.55%)  1 2/22 (9.09%)  3
URINARY TRACT INFECTION  1  0/22 (0.00%)  0 2/22 (9.09%)  2
Respiratory, thoracic and mediastinal disorders     
COUGH  1  2/22 (9.09%)  3 2/22 (9.09%)  2
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
EMail: GSKClinicalSupportHD@gsk.com
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02683785     History of Changes
Other Study ID Numbers: 204851
2015-003089-96 ( EudraCT Number )
First Submitted: January 21, 2016
First Posted: February 17, 2016
Results First Submitted: November 26, 2018
Results First Posted: December 14, 2018
Last Update Posted: April 10, 2019