Trial Outcomes & Findings for Mechanistic Study of GSK3196165 Plus Methotrexate (MTX) in Subjects With Active Rheumatoid Arthritis (NCT NCT02799472)
NCT ID: NCT02799472
Last Updated: 2021-01-11
Results Overview
Blood samples were collected for markers which may influence rheumatoid arthritis. Target engagement biomarkers included soluble GM-CSF complexed to GSK3196165. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for GM-CSF - Complex log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Analysis was performed on Intent-to-Treat (ITT) Population which consisted of all participants who were randomized to treatment and who received at least one dose of study treatment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
39 participants
Primary outcome timeframe
Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week follow-up (FU) (Week 22)
Results posted on
2021-01-11
Participant Flow
A total of 39 participants with active early/established Rheumatoid arthritis were randomized across 9 centers in 3 countries from 15 June 2016 to 30 October 2017.
Out of the 88 participants screened for this study, 49 participants were screen failures and 39 participants were randomized and received treatment in the study.
Participant milestones
| Measure |
Placebo
Eligible participants received matching placebo subcutaneously (SC) into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received methotrexate (MTX) 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
Eligible participants received GSK3196165 180 milligrams (mg) SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
28
|
|
Overall Study
COMPLETED
|
7
|
23
|
|
Overall Study
NOT COMPLETED
|
4
|
5
|
Reasons for withdrawal
| Measure |
Placebo
Eligible participants received matching placebo subcutaneously (SC) into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received methotrexate (MTX) 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
Eligible participants received GSK3196165 180 milligrams (mg) SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
4
|
|
Overall Study
Lack of Efficacy
|
2
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
Baseline Characteristics
Mechanistic Study of GSK3196165 Plus Methotrexate (MTX) in Subjects With Active Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
Total
n=39 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.3 Years
STANDARD_DEVIATION 11.57 • n=5 Participants
|
59.1 Years
STANDARD_DEVIATION 9.47 • n=7 Participants
|
56.6 Years
STANDARD_DEVIATION 10.73 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
9 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week follow-up (FU) (Week 22)Population: ITT Population.
Blood samples were collected for markers which may influence rheumatoid arthritis. Target engagement biomarkers included soluble GM-CSF complexed to GSK3196165. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for GM-CSF - Complex log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Analysis was performed on Intent-to-Treat (ITT) Population which consisted of all participants who were randomized to treatment and who received at least one dose of study treatment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Target Engagement Biomarkers- Soluble Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) Complexed to GSK3196165
GM-CSF - Complex, Week 1, n=9, 27
|
0.972 Ratio of GM-CSF complex
Geometric Coefficient of Variation 35.98
|
13.799 Ratio of GM-CSF complex
Geometric Coefficient of Variation 20.65
|
|
Change From Baseline in Target Engagement Biomarkers- Soluble Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) Complexed to GSK3196165
GM-CSF - Complex, Week 2, n=8, 26
|
0.960 Ratio of GM-CSF complex
Geometric Coefficient of Variation 31.23
|
31.056 Ratio of GM-CSF complex
Geometric Coefficient of Variation 17.58
|
|
Change From Baseline in Target Engagement Biomarkers- Soluble Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) Complexed to GSK3196165
GM-CSF - Complex, Week 4, n=8, 27
|
0.959 Ratio of GM-CSF complex
Geometric Coefficient of Variation 34.51
|
53.496 Ratio of GM-CSF complex
Geometric Coefficient of Variation 18.55
|
|
Change From Baseline in Target Engagement Biomarkers- Soluble Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) Complexed to GSK3196165
GM-CSF - Complex, Week 6, n=7, 26
|
0.964 Ratio of GM-CSF complex
Geometric Coefficient of Variation 40.96
|
46.620 Ratio of GM-CSF complex
Geometric Coefficient of Variation 22.37
|
|
Change From Baseline in Target Engagement Biomarkers- Soluble Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) Complexed to GSK3196165
GM-CSF - Complex, Week 8, n=7, 24
|
0.964 Ratio of GM-CSF complex
Geometric Coefficient of Variation 41.80
|
33.404 Ratio of GM-CSF complex
Geometric Coefficient of Variation 22.47
|
|
Change From Baseline in Target Engagement Biomarkers- Soluble Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) Complexed to GSK3196165
GM-CSF - Complex, Week 12, n=7, 24
|
0.970 Ratio of GM-CSF complex
Geometric Coefficient of Variation 44.95
|
22.556 Ratio of GM-CSF complex
Geometric Coefficient of Variation 24.38
|
|
Change From Baseline in Target Engagement Biomarkers- Soluble Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) Complexed to GSK3196165
GM-CSF - Complex, 12-Week FU, n=8, 21
|
0.954 Ratio of GM-CSF complex
Geometric Coefficient of Variation 20.80
|
1.176 Ratio of GM-CSF complex
Geometric Coefficient of Variation 12.88
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)Population: ITT Population.
Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of 14-3-3 ETA Protein, S100 CBP A8 and A9. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for 14-3-3 ETA Protein (mg/L) and S100 CBP A8 and A9 log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
14-3-3 ETA Protein, Week 1, n=9, 27
|
1.046 Ratio of predictive biomarker
Geometric Coefficient of Variation 3.88
|
0.986 Ratio of predictive biomarker
Geometric Coefficient of Variation 2.16
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
14-3-3 ETA Protein, Week 2, n=8, 26
|
0.959 Ratio of predictive biomarker
Geometric Coefficient of Variation 12.14
|
0.986 Ratio of predictive biomarker
Geometric Coefficient of Variation 6.70
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
14-3-3 ETA Protein, Week 4, n=9, 26
|
1.128 Ratio of predictive biomarker
Geometric Coefficient of Variation 16.59
|
0.838 Ratio of predictive biomarker
Geometric Coefficient of Variation 9.55
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
14-3-3 ETA Protein, Week 6, n=7, 26
|
1.093 Ratio of predictive biomarker
Geometric Coefficient of Variation 15.55
|
0.833 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.88
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
14-3-3 ETA Protein, Week 8, n=7, 23
|
0.950 Ratio of predictive biomarker
Geometric Coefficient of Variation 15.19
|
0.842 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.48
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
14-3-3 ETA Protein, Week 12, n=7, 24
|
1.131 Ratio of predictive biomarker
Geometric Coefficient of Variation 20.90
|
0.897 Ratio of predictive biomarker
Geometric Coefficient of Variation 11.89
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
14-3-3 ETA Protein, 12-Week FU, n=7, 21
|
1.040 Ratio of predictive biomarker
Geometric Coefficient of Variation 24.06
|
0.893 Ratio of predictive biomarker
Geometric Coefficient of Variation 13.45
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
S100 CBP A8 and A9, Week 1, n=9, 27
|
0.940 Ratio of predictive biomarker
Geometric Coefficient of Variation 15.20
|
0.939 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.92
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
S100 CBP A8 and A9, Week 2, n=8, 26
|
0.871 Ratio of predictive biomarker
Geometric Coefficient of Variation 15.28
|
0.823 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.65
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
S100 CBP A8 and A9, Week 4, n=9, 27
|
0.874 Ratio of predictive biomarker
Geometric Coefficient of Variation 19.20
|
0.889 Ratio of predictive biomarker
Geometric Coefficient of Variation 11.26
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
S100 CBP A8 and A9, Week 6, n=7, 27
|
0.828 Ratio of predictive biomarker
Geometric Coefficient of Variation 21.92
|
0.812 Ratio of predictive biomarker
Geometric Coefficient of Variation 11.81
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
S100 CBP A8 and A9, Week 8, n=7, 25
|
0.804 Ratio of predictive biomarker
Geometric Coefficient of Variation 21.04
|
0.857 Ratio of predictive biomarker
Geometric Coefficient of Variation 11.46
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
S100 CBP A8 and A9, Week 12, n=7, 24
|
0.694 Ratio of predictive biomarker
Geometric Coefficient of Variation 21.61
|
0.879 Ratio of predictive biomarker
Geometric Coefficient of Variation 12.05
|
|
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
S100 CBP A8 and A9, 12-Week FU, n=7, 21
|
0.582 Ratio of predictive biomarker
Geometric Coefficient of Variation 20.60
|
1.018 Ratio of predictive biomarker
Geometric Coefficient of Variation 11.83
|
PRIMARY outcome
Timeframe: Baseline and Week 12, 12-Week FU (Week 22)Population: ITT Population.
Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of Amyloid A. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for Amyloid A log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data has been presented for only those time points at which the samples were collected.
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Predictive Biomarkers: Amyloid A
Amyloid A, Week 12, n=7, 24
|
0.845 Ratio of predictive biomarker
Geometric Coefficient of Variation 49.31
|
0.653 Ratio of predictive biomarker
Geometric Coefficient of Variation 25.45
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A
Amyloid A, 12-Week FU, n=7, 21
|
0.529 Ratio of predictive biomarker
Geometric Coefficient of Variation 35.12
|
0.623 Ratio of predictive biomarker
Geometric Coefficient of Variation 19.68
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)Population: ITT Population.
Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of Chemokine (C-C Motif) Ligand 17 (CL17), Chemokine (C-X-C Motif) Ligand 13 (CL13), Interleukin 6, Macrophage-Derived Chemokine (MDC). Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for CL17, CL13, Interleukin 6, MDC log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data has been presented for only those time points at which the samples were collected.
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL13, Week 2, n=8, 26
|
1.090 Ratio of predictive biomarker
Geometric Coefficient of Variation 13.98
|
1.095 Ratio of predictive biomarker
Geometric Coefficient of Variation 7.78
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL13, Week 4, n=9, 27
|
0.947 Ratio of predictive biomarker
Geometric Coefficient of Variation 15.58
|
1.170 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.90
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL13, Week 6, n=7, 27
|
0.839 Ratio of predictive biomarker
Geometric Coefficient of Variation 17.20
|
1.038 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.91
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL13, Week 8, n=7, 25
|
0.913 Ratio of predictive biomarker
Geometric Coefficient of Variation 23.70
|
1.021 Ratio of predictive biomarker
Geometric Coefficient of Variation 12.38
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL13, Week 12, n=7,24
|
0.924 Ratio of predictive biomarker
Geometric Coefficient of Variation 31.17
|
1.077 Ratio of predictive biomarker
Geometric Coefficient of Variation 16.31
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL13, 12-Week FU, n=7,21
|
0.774 Ratio of predictive biomarker
Geometric Coefficient of Variation 27.82
|
1.224 Ratio of predictive biomarker
Geometric Coefficient of Variation 15.04
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
Interleukin 6, Week 1, n=9, 26
|
1.179 Ratio of predictive biomarker
Geometric Coefficient of Variation 27.92
|
1.064 Ratio of predictive biomarker
Geometric Coefficient of Variation 16.38
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
Interleukin 6, Week 2, n=8, 26
|
1.153 Ratio of predictive biomarker
Geometric Coefficient of Variation 29.33
|
0.830 Ratio of predictive biomarker
Geometric Coefficient of Variation 16.63
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
Interleukin 6, Week 4, n=9, 27
|
0.986 Ratio of predictive biomarker
Geometric Coefficient of Variation 26.22
|
0.811 Ratio of predictive biomarker
Geometric Coefficient of Variation 15.10
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
Interleukin 6, Week 6, n=7, 27
|
1.136 Ratio of predictive biomarker
Geometric Coefficient of Variation 24.95
|
0.748 Ratio of predictive biomarker
Geometric Coefficient of Variation 13.51
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
Interleukin 6, Week 8, n=7, 25
|
1.275 Ratio of predictive biomarker
Geometric Coefficient of Variation 23.65
|
0.872 Ratio of predictive biomarker
Geometric Coefficient of Variation 13.35
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
Interleukin 6, Week 12, n=7, 24
|
0.770 Ratio of predictive biomarker
Geometric Coefficient of Variation 21.89
|
0.939 Ratio of predictive biomarker
Geometric Coefficient of Variation 12.35
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
Interleukin 6, 12-Week FU, n=7, 21
|
0.817 Ratio of predictive biomarker
Geometric Coefficient of Variation 33.13
|
1.308 Ratio of predictive biomarker
Geometric Coefficient of Variation 18.63
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
MDC, Week 1, n=9, 27
|
0.987 Ratio of predictive biomarker
Geometric Coefficient of Variation 5.02
|
0.914 Ratio of predictive biomarker
Geometric Coefficient of Variation 2.89
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
MDC, Week 2, n=8, 26
|
0.925 Ratio of predictive biomarker
Geometric Coefficient of Variation 7.33
|
0.911 Ratio of predictive biomarker
Geometric Coefficient of Variation 4.15
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
MDC, Week 4, n=9, 27
|
0.936 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.13
|
0.895 Ratio of predictive biomarker
Geometric Coefficient of Variation 4.67
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
MDC, Week 6, n=7, 27
|
0.984 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.38
|
0.994 Ratio of predictive biomarker
Geometric Coefficient of Variation 4.48
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
MDC, Week 8, n=7, 25
|
1.049 Ratio of predictive biomarker
Geometric Coefficient of Variation 9.36
|
0.899 Ratio of predictive biomarker
Geometric Coefficient of Variation 5.09
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
MDC, Week 12, n=7, 24
|
1.245 Ratio of predictive biomarker
Geometric Coefficient of Variation 9.51
|
1.058 Ratio of predictive biomarker
Geometric Coefficient of Variation 5.23
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
MDC, 12-Week FU, n=7, 20
|
1.303 Ratio of predictive biomarker
Geometric Coefficient of Variation 12.66
|
1.321 Ratio of predictive biomarker
Geometric Coefficient of Variation 7.53
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL17, Week 2, n=8, 26
|
0.912 Ratio of predictive biomarker
Geometric Coefficient of Variation 24.37
|
0.651 Ratio of predictive biomarker
Geometric Coefficient of Variation 13.60
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL17, Week 1, n=9, 27
|
1.117 Ratio of predictive biomarker
Geometric Coefficient of Variation 18.81
|
0.773 Ratio of predictive biomarker
Geometric Coefficient of Variation 10.94
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL17, Week 4, n=9, 27
|
1.117 Ratio of predictive biomarker
Geometric Coefficient of Variation 21.91
|
0.679 Ratio of predictive biomarker
Geometric Coefficient of Variation 12.51
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL17, Week 6, n=7, 27
|
1.032 Ratio of predictive biomarker
Geometric Coefficient of Variation 24.38
|
0.779 Ratio of predictive biomarker
Geometric Coefficient of Variation 12.48
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL17, Week 8, n=7, 25
|
1.211 Ratio of predictive biomarker
Geometric Coefficient of Variation 20.63
|
0.675 Ratio of predictive biomarker
Geometric Coefficient of Variation 11.21
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL17, Week 12, n=7, 24
|
1.711 Ratio of predictive biomarker
Geometric Coefficient of Variation 24.96
|
0.890 Ratio of predictive biomarker
Geometric Coefficient of Variation 13.90
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL17, 12-Week FU, n=7, 20
|
1.434 Ratio of predictive biomarker
Geometric Coefficient of Variation 23.26
|
1.357 Ratio of predictive biomarker
Geometric Coefficient of Variation 13.59
|
|
Change From Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
CL13, Week 1, n=9, 27
|
1.198 Ratio of predictive biomarker
Geometric Coefficient of Variation 15.63
|
0.915 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.87
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)Population: ITT Population.
Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of Chitinase 3 Like 1 and MMP-3. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for Chitinase 3 Like 1 and MMP-3 log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
MMP-3, Week 2, n=8, 26
|
1.067 Ratio of predictive biomarker
Geometric Coefficient of Variation 7.26
|
1.024 Ratio of predictive biomarker
Geometric Coefficient of Variation 4.09
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
Chitinase 3 Like 1, Week 1, n=9, 27
|
1.033 Ratio of predictive biomarker
Geometric Coefficient of Variation 13.97
|
0.917 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.13
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
Chitinase 3 Like 1, Week 2, n=8, 26
|
1.013 Ratio of predictive biomarker
Geometric Coefficient of Variation 15.05
|
0.966 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.55
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
Chitinase 3 Like 1, Week 4, n=9, 27
|
0.961 Ratio of predictive biomarker
Geometric Coefficient of Variation 17.14
|
1.088 Ratio of predictive biomarker
Geometric Coefficient of Variation 9.96
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
Chitinase 3 Like 1, Week 6, n=7, 27
|
0.897 Ratio of predictive biomarker
Geometric Coefficient of Variation 17.08
|
1.031 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.80
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
Chitinase 3 Like 1, Week 8, n=7, 25
|
0.851 Ratio of predictive biomarker
Geometric Coefficient of Variation 18.24
|
0.947 Ratio of predictive biomarker
Geometric Coefficient of Variation 9.70
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
Chitinase 3 Like 1, Week 12, n=7, 24
|
1.066 Ratio of predictive biomarker
Geometric Coefficient of Variation 21.53
|
1.071 Ratio of predictive biomarker
Geometric Coefficient of Variation 11.64
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
Chitinase 3 Like 1, 12-Week FU, n=7, 21
|
0.735 Ratio of predictive biomarker
Geometric Coefficient of Variation 16.87
|
1.019 Ratio of predictive biomarker
Geometric Coefficient of Variation 9.75
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
MMP 3, Week 1, n=9, 27
|
1.076 Ratio of predictive biomarker
Geometric Coefficient of Variation 6.72
|
0.984 Ratio of predictive biomarker
Geometric Coefficient of Variation 3.88
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
MMP-3, Week 4, n=9, 27
|
1.112 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.30
|
1.016 Ratio of predictive biomarker
Geometric Coefficient of Variation 4.73
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
MMP-3, Week 6, n=7, 27
|
1.005 Ratio of predictive biomarker
Geometric Coefficient of Variation 26.26
|
0.804 Ratio of predictive biomarker
Geometric Coefficient of Variation 13.44
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
MMP-3, Week 8, n=7, 25
|
0.939 Ratio of predictive biomarker
Geometric Coefficient of Variation 15.43
|
1.088 Ratio of predictive biomarker
Geometric Coefficient of Variation 8.21
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
MMP-3, Week 12, n=7, 24
|
1.000 Ratio of predictive biomarker
Geometric Coefficient of Variation 13.57
|
0.951 Ratio of predictive biomarker
Geometric Coefficient of Variation 7.35
|
|
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
MMP-3, 12-Week FU, n=7, 21
|
0.803 Ratio of predictive biomarker
Geometric Coefficient of Variation 16.05
|
0.984 Ratio of predictive biomarker
Geometric Coefficient of Variation 9.00
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)Population: ITT Population.
Blood samples were collected and analyzed for markers that may be predictive of rheumatoid arthritis disease activity. Cartilage biomarkers included analysis of ARGS Neo-Epitope, Citrullinated MMP-Degraded Vimentin (CMDV), MMP-Degraded C Reactive Protein (CRP), MMP-Degraded Type I Collagen (MD1C), MMP-Degraded Type II Collagen (MD2C), MMP-Degraded Type III Collagen (MD3C). Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for ARGS Neo-Epitope, Citrullinated MMP-Degraded Vimentin, MMP-Degraded CRP, MMP-Degraded Type I Collagen, MMP-Degraded Type II Collagen and MMP-Degraded Type III Collagen log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Cartilage Biomarkers
ARGS Neo-Epitope, Week 2, n=8, 25
|
0.790 Ratio of cartilage biomarker
Geometric Coefficient of Variation 17.38
|
1.249 Ratio of cartilage biomarker
Geometric Coefficient of Variation 9.87
|
|
Change From Baseline in Cartilage Biomarkers
CMDV, Week 8,n=7,25
|
0.929 Ratio of cartilage biomarker
Geometric Coefficient of Variation 24.72
|
0.759 Ratio of cartilage biomarker
Geometric Coefficient of Variation 13.39
|
|
Change From Baseline in Cartilage Biomarkers
MMP-Degraded CRP, Week 4, n=9, 27
|
0.992 Ratio of cartilage biomarker
Geometric Coefficient of Variation 6.01
|
1.004 Ratio of cartilage biomarker
Geometric Coefficient of Variation 3.49
|
|
Change From Baseline in Cartilage Biomarkers
MMP-Degraded CRP, Week 12, n=7, 24
|
1.006 Ratio of cartilage biomarker
Geometric Coefficient of Variation 7.13
|
1.108 Ratio of cartilage biomarker
Geometric Coefficient of Variation 3.95
|
|
Change From Baseline in Cartilage Biomarkers
MD2C, Week 12, n=7, 24
|
1.174 Ratio of cartilage biomarker
Geometric Coefficient of Variation 10.73
|
1.072 Ratio of cartilage biomarker
Geometric Coefficient of Variation 5.87
|
|
Change From Baseline in Cartilage Biomarkers
MD2C, 12-Week FU, n=7, 21
|
1.338 Ratio of cartilage biomarker
Geometric Coefficient of Variation 13.10
|
1.041 Ratio of cartilage biomarker
Geometric Coefficient of Variation 7.50
|
|
Change From Baseline in Cartilage Biomarkers
MD3C, Week 1, n=9, 27
|
0.950 Ratio of cartilage biomarker
Geometric Coefficient of Variation 6.44
|
0.959 Ratio of cartilage biomarker
Geometric Coefficient of Variation 3.74
|
|
Change From Baseline in Cartilage Biomarkers
MD3C, Week 4, n=9, 27
|
0.940 Ratio of cartilage biomarker
Geometric Coefficient of Variation 8.06
|
0.886 Ratio of cartilage biomarker
Geometric Coefficient of Variation 4.68
|
|
Change From Baseline in Cartilage Biomarkers
MD3C, Week 6, n=7, 27
|
1.013 Ratio of cartilage biomarker
Geometric Coefficient of Variation 8.09
|
0.894 Ratio of cartilage biomarker
Geometric Coefficient of Variation 4.34
|
|
Change From Baseline in Cartilage Biomarkers
MD3C, Week 8, n=7, 25
|
0.918 Ratio of cartilage biomarker
Geometric Coefficient of Variation 9.04
|
0.881 Ratio of cartilage biomarker
Geometric Coefficient of Variation 4.84
|
|
Change From Baseline in Cartilage Biomarkers
MD3C, Week 12, n=7, 24
|
0.929 Ratio of cartilage biomarker
Geometric Coefficient of Variation 9.28
|
0.910 Ratio of cartilage biomarker
Geometric Coefficient of Variation 5.08
|
|
Change From Baseline in Cartilage Biomarkers
ARGS Neo-Epitope, Week 1, n=9, 27
|
0.979 Ratio of cartilage biomarker
Geometric Coefficient of Variation 16.10
|
1.075 Ratio of cartilage biomarker
Geometric Coefficient of Variation 9.67
|
|
Change From Baseline in Cartilage Biomarkers
ARGS Neo-Epitope, Week 4, n=8, 26
|
0.904 Ratio of cartilage biomarker
Geometric Coefficient of Variation 17.02
|
1.104 Ratio of cartilage biomarker
Geometric Coefficient of Variation 10.05
|
|
Change From Baseline in Cartilage Biomarkers
ARGS Neo-Epitope, Week 6, n=6, 26
|
0.894 Ratio of cartilage biomarker
Geometric Coefficient of Variation 14.28
|
1.164 Ratio of cartilage biomarker
Geometric Coefficient of Variation 7.82
|
|
Change From Baseline in Cartilage Biomarkers
ARGS Neo-Epitope, Week 8, n=7, 24
|
0.854 Ratio of cartilage biomarker
Geometric Coefficient of Variation 26.42
|
1.238 Ratio of cartilage biomarker
Geometric Coefficient of Variation 14.20
|
|
Change From Baseline in Cartilage Biomarkers
ARGS Neo-Epitope, Week 12, n=7, 24
|
0.913 Ratio of cartilage biomarker
Geometric Coefficient of Variation 13.97
|
1.156 Ratio of cartilage biomarker
Geometric Coefficient of Variation 7.78
|
|
Change From Baseline in Cartilage Biomarkers
ARGS Neo-Epitope, 12-Week FU, n=8, 21
|
1.129 Ratio of cartilage biomarker
Geometric Coefficient of Variation 17.44
|
1.124 Ratio of cartilage biomarker
Geometric Coefficient of Variation 9.86
|
|
Change From Baseline in Cartilage Biomarkers
CMDV, Week 1,n=9,27
|
0.981 Ratio of cartilage biomarker
Geometric Coefficient of Variation 24.12
|
0.876 Ratio of cartilage biomarker
Geometric Coefficient of Variation 13.80
|
|
Change From Baseline in Cartilage Biomarkers
CMDV,Week 2,n=8,26
|
0.820 Ratio of cartilage biomarker
Geometric Coefficient of Variation 28.46
|
0.714 Ratio of cartilage biomarker
Geometric Coefficient of Variation 15.89
|
|
Change From Baseline in Cartilage Biomarkers
CMDV, Week 4,n=9,27
|
0.715 Ratio of cartilage biomarker
Geometric Coefficient of Variation 27.30
|
0.801 Ratio of cartilage biomarker
Geometric Coefficient of Variation 15.52
|
|
Change From Baseline in Cartilage Biomarkers
CMDV, Week 6,n=7,27
|
1.099 Ratio of cartilage biomarker
Geometric Coefficient of Variation 30.47
|
0.726 Ratio of cartilage biomarker
Geometric Coefficient of Variation 15.94
|
|
Change From Baseline in Cartilage Biomarkers
CMDV, Week12,n=7,24
|
1.123 Ratio of cartilage biomarker
Geometric Coefficient of Variation 29.34
|
0.917 Ratio of cartilage biomarker
Geometric Coefficient of Variation 16.00
|
|
Change From Baseline in Cartilage Biomarkers
CMDV, 12-Week FU,n=7,21
|
0.936 Ratio of cartilage biomarker
Geometric Coefficient of Variation 28.05
|
0.769 Ratio of cartilage biomarker
Geometric Coefficient of Variation 15.81
|
|
Change From Baseline in Cartilage Biomarkers
MMP-Degraded CRP, Week 1, n=9, 27
|
0.971 Ratio of cartilage biomarker
Geometric Coefficient of Variation 6.83
|
1.021 Ratio of cartilage biomarker
Geometric Coefficient of Variation 3.99
|
|
Change From Baseline in Cartilage Biomarkers
MMP-Degraded CRP, Week 2, n=8, 26
|
0.970 Ratio of cartilage biomarker
Geometric Coefficient of Variation 5.55
|
1.000 Ratio of cartilage biomarker
Geometric Coefficient of Variation 3.07
|
|
Change From Baseline in Cartilage Biomarkers
MMP-Degraded CRP, Week 6, n=7, 27
|
1.122 Ratio of cartilage biomarker
Geometric Coefficient of Variation 6.55
|
1.099 Ratio of cartilage biomarker
Geometric Coefficient of Variation 3.50
|
|
Change From Baseline in Cartilage Biomarkers
MMP-Degraded CRP, Week 8, n=7, 25
|
0.977 Ratio of cartilage biomarker
Geometric Coefficient of Variation 7.37
|
1.087 Ratio of cartilage biomarker
Geometric Coefficient of Variation 4.05
|
|
Change From Baseline in Cartilage Biomarkers
MMP-Degraded CRP, 12-Week FU, n=7, 21
|
1.075 Ratio of cartilage biomarker
Geometric Coefficient of Variation 8.01
|
1.129 Ratio of cartilage biomarker
Geometric Coefficient of Variation 4.48
|
|
Change From Baseline in Cartilage Biomarkers
MD1C, Week 1, n=9, 27
|
1.079 Ratio of cartilage biomarker
Geometric Coefficient of Variation 9.60
|
0.858 Ratio of cartilage biomarker
Geometric Coefficient of Variation 5.63
|
|
Change From Baseline in Cartilage Biomarkers
MD1C, Week 2, n=8, 26
|
1.028 Ratio of cartilage biomarker
Geometric Coefficient of Variation 11.98
|
0.907 Ratio of cartilage biomarker
Geometric Coefficient of Variation 6.63
|
|
Change From Baseline in Cartilage Biomarkers
MD1C, Week 4, n=9, 27
|
1.142 Ratio of cartilage biomarker
Geometric Coefficient of Variation 14.57
|
0.896 Ratio of cartilage biomarker
Geometric Coefficient of Variation 8.35
|
|
Change From Baseline in Cartilage Biomarkers
MD1C, Week 6, n=7, 27
|
1.392 Ratio of cartilage biomarker
Geometric Coefficient of Variation 12.64
|
0.889 Ratio of cartilage biomarker
Geometric Coefficient of Variation 6.98
|
|
Change From Baseline in Cartilage Biomarkers
MD1C, Week 8, n=7, 25
|
1.131 Ratio of cartilage biomarker
Geometric Coefficient of Variation 13.05
|
0.904 Ratio of cartilage biomarker
Geometric Coefficient of Variation 7.23
|
|
Change From Baseline in Cartilage Biomarkers
MD1C, Week 12, n=7, 24
|
1.148 Ratio of cartilage biomarker
Geometric Coefficient of Variation 13.74
|
1.023 Ratio of cartilage biomarker
Geometric Coefficient of Variation 7.81
|
|
Change From Baseline in Cartilage Biomarkers
MD1C, 12-Week FU, n=7, 21
|
1.095 Ratio of cartilage biomarker
Geometric Coefficient of Variation 14.21
|
0.952 Ratio of cartilage biomarker
Geometric Coefficient of Variation 8.31
|
|
Change From Baseline in Cartilage Biomarkers
MD2C, Week 1, n=9, 27
|
1.059 Ratio of cartilage biomarker
Geometric Coefficient of Variation 11.83
|
1.038 Ratio of cartilage biomarker
Geometric Coefficient of Variation 6.88
|
|
Change From Baseline in Cartilage Biomarkers
MD2C, Week 2, n=8, 26
|
1.046 Ratio of cartilage biomarker
Geometric Coefficient of Variation 11.27
|
1.015 Ratio of cartilage biomarker
Geometric Coefficient of Variation 6.28
|
|
Change From Baseline in Cartilage Biomarkers
MD2C, Week 4, n=9, 27
|
1.035 Ratio of cartilage biomarker
Geometric Coefficient of Variation 10.18
|
1.003 Ratio of cartilage biomarker
Geometric Coefficient of Variation 5.86
|
|
Change From Baseline in Cartilage Biomarkers
MD2C, Week 6, n=7, 27
|
1.158 Ratio of cartilage biomarker
Geometric Coefficient of Variation 12.07
|
1.064 Ratio of cartilage biomarker
Geometric Coefficient of Variation 6.30
|
|
Change From Baseline in Cartilage Biomarkers
MD2C, Week 8, n=7, 25
|
1.091 Ratio of cartilage biomarker
Geometric Coefficient of Variation 11.42
|
1.023 Ratio of cartilage biomarker
Geometric Coefficient of Variation 6.12
|
|
Change From Baseline in Cartilage Biomarkers
MD3C, Week 2, n=8, 26
|
0.920 Ratio of cartilage biomarker
Geometric Coefficient of Variation 6.82
|
0.954 Ratio of cartilage biomarker
Geometric Coefficient of Variation 3.91
|
|
Change From Baseline in Cartilage Biomarkers
MD3C, 12-Week FU, n=7, 21
|
0.847 Ratio of cartilage biomarker
Geometric Coefficient of Variation 9.75
|
0.910 Ratio of cartilage biomarker
Geometric Coefficient of Variation 5.46
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)Population: ITT Population.
Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of Helper/Suppressor. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for Helper/Suppressor log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Flow Cytometry: Helper/Suppressor Cells
Helper/Suppressor, Week 1, n=8, 25
|
1.024 Ratio of Helper/Suppressor cells
Geometric Coefficient of Variation 6.98
|
0.976 Ratio of Helper/Suppressor cells
Geometric Coefficient of Variation 4.00
|
|
Change From Baseline in Flow Cytometry: Helper/Suppressor Cells
Helper/Suppressor, Week 4, n=8, 25
|
1.053 Ratio of Helper/Suppressor cells
Geometric Coefficient of Variation 7.18
|
0.998 Ratio of Helper/Suppressor cells
Geometric Coefficient of Variation 4.11
|
|
Change From Baseline in Flow Cytometry: Helper/Suppressor Cells
Helper/Suppressor, Week 12, n=6, 25
|
1.040 Ratio of Helper/Suppressor cells
Geometric Coefficient of Variation 6.83
|
1.088 Ratio of Helper/Suppressor cells
Geometric Coefficient of Variation 3.49
|
|
Change From Baseline in Flow Cytometry: Helper/Suppressor Cells
Helper/Suppressor, 12-Week FU, n=6, 21
|
1.051 Ratio of Helper/Suppressor cells
Geometric Coefficient of Variation 8.99
|
1.065 Ratio of Helper/Suppressor cells
Geometric Coefficient of Variation 4.88
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)Population: ITT Population.
Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of cluster of differentiation (CD)16+CD56+, CD19, CD3, CD3+CD4+. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Repeated measures analysis adjusted for CD16+CD56+, CD19, CD3, CD3+CD4+, CD3+CD8+ and T Cell B Cell NKL log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD16+CD56+, Week 1, n=8, 25
|
0.989 Ratio of biomarker
Geometric Coefficient of Variation 11.39
|
1.025 Ratio of biomarker
Geometric Coefficient of Variation 6.30
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD16+CD56+, Week 4, n=8, 25
|
1.163 Ratio of biomarker
Geometric Coefficient of Variation 12.97
|
0.951 Ratio of biomarker
Geometric Coefficient of Variation 7.25
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD16+CD56+, Week 12, n=6, 25
|
1.193 Ratio of biomarker
Geometric Coefficient of Variation 15.49
|
0.911 Ratio of biomarker
Geometric Coefficient of Variation 7.81
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD16+CD56+, 12-Week FU, n=6, 21
|
1.298 Ratio of biomarker
Geometric Coefficient of Variation 15.10
|
0.920 Ratio of biomarker
Geometric Coefficient of Variation 7.98
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD19, Week 1, n=8, 25
|
0.880 Ratio of biomarker
Geometric Coefficient of Variation 11.05
|
0.984 Ratio of biomarker
Geometric Coefficient of Variation 6.23
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD19, Week 4, n=8, 25
|
1.090 Ratio of biomarker
Geometric Coefficient of Variation 15.31
|
0.971 Ratio of biomarker
Geometric Coefficient of Variation 8.60
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD19, Week 12, n=6, 25
|
1.054 Ratio of biomarker
Geometric Coefficient of Variation 12.26
|
1.003 Ratio of biomarker
Geometric Coefficient of Variation 6.51
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD19, Week 22, n=6, 21
|
0.980 Ratio of biomarker
Geometric Coefficient of Variation 17.75
|
0.938 Ratio of biomarker
Geometric Coefficient of Variation 9.75
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD3, Week 1, n=8, 25
|
0.918 Ratio of biomarker
Geometric Coefficient of Variation 8.73
|
0.994 Ratio of biomarker
Geometric Coefficient of Variation 4.95
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD3, Week 4, n=8, 25
|
0.997 Ratio of biomarker
Geometric Coefficient of Variation 11.79
|
0.934 Ratio of biomarker
Geometric Coefficient of Variation 6.66
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD3, Week 12, n=6, 25
|
0.912 Ratio of biomarker
Geometric Coefficient of Variation 9.01
|
0.992 Ratio of biomarker
Geometric Coefficient of Variation 4.60
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD3, 12-Week FU, n=6, 21
|
0.931 Ratio of biomarker
Geometric Coefficient of Variation 9.17
|
0.989 Ratio of biomarker
Geometric Coefficient of Variation 4.98
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD3+CD4+, Week 1, n=8, 25
|
0.926 Ratio of biomarker
Geometric Coefficient of Variation 9.56
|
0.991 Ratio of biomarker
Geometric Coefficient of Variation 5.42
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD3+CD4+, Week 4, n=8, 25
|
1.028 Ratio of biomarker
Geometric Coefficient of Variation 12.80
|
0.933 Ratio of biomarker
Geometric Coefficient of Variation 7.23
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD3+CD4+, Week 12, n=6, 25
|
0.952 Ratio of biomarker
Geometric Coefficient of Variation 9.69
|
1.013 Ratio of biomarker
Geometric Coefficient of Variation 4.94
|
|
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
CD3+CD4+, 12-Week FU, n=6, 21
|
0.970 Ratio of biomarker
Geometric Coefficient of Variation 9.92
|
1.000 Ratio of biomarker
Geometric Coefficient of Variation 5.37
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)Population: ITT Population.
Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of CD3+CD8+ and T Cell B Cell NKL. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for CD3+CD8+ and T Cell B Cell NKL log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL)
CD3+CD8+, Week 12, n=6, 25
|
-0.056 10^9 cells/Liter
Standard Error 0.0418
|
-0.037 10^9 cells/Liter
Standard Error 0.0215
|
|
Change From Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL)
T Cell B Cell NKL, Week 12, n=6, 25
|
-0.093 10^9 cells/Liter
Standard Error 0.1792
|
-0.006 10^9 cells/Liter
Standard Error 0.0925
|
|
Change From Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL)
CD3+CD8+, Week 1, n=8, 25
|
-0.041 10^9 cells/Liter
Standard Error 0.0390
|
-0.005 10^9 cells/Liter
Standard Error 0.0222
|
|
Change From Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL)
CD3+CD8+, Week 4, n=8, 25
|
0.000 10^9 cells/Liter
Standard Error 0.0580
|
-0.023 10^9 cells/Liter
Standard Error 0.0327
|
|
Change From Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL)
CD3+CD8+, 12-Week FU, n=6, 21
|
-0.060 10^9 cells/Liter
Standard Error 0.0506
|
-0.027 10^9 cells/Liter
Standard Error 0.0279
|
|
Change From Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL)
T Cell B Cell NKL, Week 1, n=8, 25
|
-0.123 10^9 cells/Liter
Standard Error 0.1557
|
-0.020 10^9 cells/Liter
Standard Error 0.0881
|
|
Change From Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL)
T Cell B Cell NKL, Week 4, n=8, 25
|
0.108 10^9 cells/Liter
Standard Error 0.2174
|
-0.050 10^9 cells/Liter
Standard Error 0.1229
|
|
Change From Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL)
T Cell B Cell NKL, 12-Week FU, n=6, 21
|
-0.029 10^9 cells/Liter
Standard Error 0.2168
|
-0.050 10^9 cells/Liter
Standard Error 0.1183
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)Population: ITT Population.
Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of CD3+ CD4+, CD3+ CD8+ and CD3+. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for CD3+ CD4+, CD3+ CD8+ and CD3+ Number of Cells (10\^6/L) log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+ CD4+, Week 1, n=7, 23
|
0.905 Ratio of T Reg cell
Geometric Coefficient of Variation 10.21
|
1.007 Ratio of T Reg cell
Geometric Coefficient of Variation 5.65
|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+ CD8+, Week 12, n=5, 21
|
0.878 Ratio of T Reg cell
Geometric Coefficient of Variation 10.50
|
0.945 Ratio of T Reg cell
Geometric Coefficient of Variation 5.40
|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+ CD8+, 12-Week FU, n=5, 17
|
0.936 Ratio of T Reg cell
Geometric Coefficient of Variation 10.99
|
0.965 Ratio of T Reg cell
Geometric Coefficient of Variation 6.05
|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+, Week 4, n=7, 22
|
1.034 Ratio of T Reg cell
Geometric Coefficient of Variation 12.99
|
0.938 Ratio of T Reg cell
Geometric Coefficient of Variation 7.33
|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+, 12-Week FU, n=5, 17
|
0.944 Ratio of T Reg cell
Geometric Coefficient of Variation 10.88
|
0.991 Ratio of T Reg cell
Geometric Coefficient of Variation 6.00
|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+ CD4+, Week 4, n=7, 22
|
1.038 Ratio of T Reg cell
Geometric Coefficient of Variation 11.31
|
0.976 Ratio of T Reg cell
Geometric Coefficient of Variation 6.38
|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+ CD4+, Week 12, n=5, 21
|
0.981 Ratio of T Reg cell
Geometric Coefficient of Variation 10.55
|
1.004 Ratio of T Reg cell
Geometric Coefficient of Variation 5.31
|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+ CD4+, 12-Week FU, n=5, 17
|
0.926 Ratio of T Reg cell
Geometric Coefficient of Variation 11.70
|
1.003 Ratio of T Reg cell
Geometric Coefficient of Variation 6.39
|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+ CD8+, Week 1, n=7, 23
|
0.885 Ratio of T Reg cell
Geometric Coefficient of Variation 9.97
|
0.983 Ratio of T Reg cell
Geometric Coefficient of Variation 5.50
|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+ CD8+, Week 4, n=7, 22
|
0.981 Ratio of T Reg cell
Geometric Coefficient of Variation 11.89
|
0.939 Ratio of T Reg cell
Geometric Coefficient of Variation 6.66
|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+, Week 1, n=7, 23
|
0.901 Ratio of T Reg cell
Geometric Coefficient of Variation 9.98
|
0.992 Ratio of T Reg cell
Geometric Coefficient of Variation 5.54
|
|
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
CD3+, Week 12, n=5, 21
|
0.959 Ratio of T Reg cell
Geometric Coefficient of Variation 9.62
|
0.993 Ratio of T Reg cell
Geometric Coefficient of Variation 4.90
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)Population: ITT Population.
Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of CD3+CD4+CD25+CD127- and CD3+CD4+foxP3+CD25+CD127-. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for CD3+CD4+CD25+CD127- and CD3+CD4+foxP3+CD25+CD127-Number of Cells (10\^6 cells/L) log(Baseline value), treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127-
CD3+CD4+CD25+CD127-, Week 1, n=7, 23
|
-3.6 10^6 cells/Liter
Standard Error 8.35
|
2.9 10^6 cells/Liter
Standard Error 4.67
|
|
Change From Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127-
CD3+CD4+CD25+CD127-, Week 4, n=7, 22
|
1.4 10^6 cells/Liter
Standard Error 8.34
|
-0.4 10^6 cells/Liter
Standard Error 4.70
|
|
Change From Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127-
CD3+CD4+CD25+CD127-, 12-Week FU, n=5, 17
|
-12.9 10^6 cells/Liter
Standard Error 9.92
|
-2.3 10^6 cells/Liter
Standard Error 5.43
|
|
Change From Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127-
CD3+CD4+CD25+CD127-, Week 12, n=5, 21
|
-9.4 10^6 cells/Liter
Standard Error 9.87
|
-3.1 10^6 cells/Liter
Standard Error 4.94
|
|
Change From Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127-
CD3+CD4+foxP3+CD25+CD127, Week 1, n=7, 23
|
0.8 10^6 cells/Liter
Standard Error 6.39
|
2.8 10^6 cells/Liter
Standard Error 3.58
|
|
Change From Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127-
CD3+CD4+foxP3+CD25+CD127, Week 4, n=7, 22
|
4.3 10^6 cells/Liter
Standard Error 7.05
|
2.0 10^6 cells/Liter
Standard Error 3.98
|
|
Change From Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127-
CD3+CD4+foxP3+CD25+CD127, Week 12, n=5, 21
|
2.7 10^6 cells/Liter
Standard Error 7.99
|
-4.4 10^6 cells/Liter
Standard Error 3.91
|
|
Change From Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127-
CD3+CD4+foxP3+CD25+CD127,12-Week FU, n=5,17
|
-8.7 10^6 cells/Liter
Standard Error 5.94
|
-4.6 10^6 cells/Liter
Standard Error 3.15
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)Population: ITT Population.
Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. T Helper Cell Panel included analysis of CD45+3+8-4+CCR6+CXCR3+38+DR+, CD45+3+8-4+CCR6+CXCR3-38+DR+, CD45+3+8-4+CCR6-CXCR3+38+DR+, CD45+3+8-4+CCR6-CXCR3-38+DR+, CD45+CD3+CD8-CD4+, CD45+CD3+CD8-CD4+CCR6+CXCR3+, CD45+CD3+CD8-CD4+CCR6+CXCR3-, CD45+CD3+CD8-CD4+CCR6-CXCR3+ and CD45+CD3+CD8-CD4+CCR6-CXCR3-. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for T Helper Cell Panel Events (EVENTS) Baseline value, treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 1, n=7, 23
|
-17.0 Events
Standard Error 6.80
|
-10.5 Events
Standard Error 3.62
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 12, n=5, 22
|
3.4 Events
Standard Error 16.09
|
-3.0 Events
Standard Error 7.55
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 1, n=7, 23
|
-73.2 Events
Standard Error 82.46
|
-129.2 Events
Standard Error 46.04
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 1, n=7, 23
|
-70.9 Events
Standard Error 25.90
|
-70.5 Events
Standard Error 14.03
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6-CXCR3-38+DR+, 12-Week FU, n=5, 18
|
-12.7 Events
Standard Error 33.50
|
-59.9 Events
Standard Error 17.32
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 4, n=7, 21
|
-116.6 Events
Standard Error 757.58
|
-316.5 Events
Standard Error 438.76
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6-CXCR3-, 12-Week FU, n=5, 18
|
-106.6 Events
Standard Error 1690.64
|
-1316.7 Events
Standard Error 892.55
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 1, n=7, 23
|
-48.6 Events
Standard Error 13.50
|
-34.0 Events
Standard Error 7.35
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 4, n=7, 21
|
-14.5 Events
Standard Error 18.36
|
-6.1 Events
Standard Error 10.63
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 12, n=5, 22
|
42.3 Events
Standard Error 37.80
|
-6.9 Events
Standard Error 17.69
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6+CXCR3+38+DR+,12-Week FU,n=5,18
|
11.5 Events
Standard Error 16.47
|
-18.7 Events
Standard Error 8.66
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 4, n=7, 21
|
14.2 Events
Standard Error 15.65
|
12.2 Events
Standard Error 9.10
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6+CXCR3-38+DR+, 12-Week FU, n=5, 18
|
8.9 Events
Standard Error 12.29
|
3.3 Events
Standard Error 6.36
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 4, n=7, 21
|
-159.6 Events
Standard Error 60.51
|
-108.0 Events
Standard Error 35.05
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 12, n=5, 22
|
219.2 Events
Standard Error 299.65
|
77.7 Events
Standard Error 146.73
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6-CXCR3+38+DR+, 12-Week FU, n=5, 18
|
33.9 Events
Standard Error 66.09
|
-104.0 Events
Standard Error 34.73
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 4, n=7, 21
|
-38.9 Events
Standard Error 30.69
|
-56.3 Events
Standard Error 17.93
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 12, n=5, 22
|
-16.4 Events
Standard Error 198.13
|
43.0 Events
Standard Error 92.38
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+, Week 1, n=7, 23
|
-3845.3 Events
Standard Error 2648.60
|
-163.0 Events
Standard Error 1444.61
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+, Week 4, n=7, 21
|
1622.8 Events
Standard Error 2973.60
|
1075.1 Events
Standard Error 1723.09
|
|
Change From Baseline in T Helper Cell Panel Events
vCD45+CD3+CD8-CD4+, Week 12, n=5, 22
|
2112.9 Events
Standard Error 4211.63
|
1006.9 Events
Standard Error 2026.47
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+, 12-Week FU, n=5, 18
|
1799.0 Events
Standard Error 2589.05
|
-1832.0 Events
Standard Error 1366.65
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 1, n=7, 23
|
-514.6 Events
Standard Error 647.85
|
-1030.2 Events
Standard Error 345.07
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 12, n=5, 22
|
-252.9 Events
Standard Error 827.53
|
-506.4 Events
Standard Error 389.97
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6+CXCR3+, 12-Week FU, n=5, 18
|
-688.1 Events
Standard Error 792.26
|
-463.0 Events
Standard Error 412.22
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 1, n=7, 23
|
-817.1 Events
Standard Error 393.10
|
-654.5 Events
Standard Error 212.18
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 4, n=7, 21
|
197.7 Events
Standard Error 475.88
|
14.2 Events
Standard Error 277.06
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 12, n=5, 22
|
48.8 Events
Standard Error 541.14
|
-219.7 Events
Standard Error 253.92
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6+CXCR3-, 12-Week FU, n=5, 18
|
-311.6 Events
Standard Error 553.32
|
-509.2 Events
Standard Error 291.09
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 1, n=7, 23
|
371.8 Events
Standard Error 1026.17
|
1521.8 Events
Standard Error 547.18
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 4, n=7, 21
|
-24.5 Events
Standard Error 1678.23
|
-292.5 Events
Standard Error 967.00
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 12, n=5, 22
|
2790.5 Events
Standard Error 2510.67
|
1443.1 Events
Standard Error 1209.66
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6-CXCR3+, 12-Week FU, n=5, 18
|
2295.9 Events
Standard Error 1787.02
|
607.0 Events
Standard Error 927.11
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 1, n=7, 23
|
-3231.4 Events
Standard Error 2162.58
|
45.4 Events
Standard Error 1187.37
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 4, n=7, 21
|
2084.9 Events
Standard Error 2873.95
|
1637.6 Events
Standard Error 1665.46
|
|
Change From Baseline in T Helper Cell Panel Events
CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 12, n=5, 22
|
-1273.9 Events
Standard Error 2413.90
|
161.4 Events
Standard Error 1209.82
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)Population: ITT Population.
Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16- and CD14lo+CD16br+. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16- and CD14lo+CD16br+ (10\^3/Liter) baseline value, treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14br+CD16+, Week 4, n=6, 22
|
-5635.3 10^3 cells/Liter
Standard Error 5971.99
|
2724.3 10^3 cells/Liter
Standard Error 3117.17
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14br+CD16+, 12-Week FU, n=5, 18
|
8557.2 10^3 cells/Liter
Standard Error 9914.93
|
4800.0 10^3 cells/Liter
Standard Error 5266.23
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14br+CD16-, Week 1, n=5, 18
|
40079.7 10^3 cells/Liter
Standard Error 40456.86
|
17662.7 10^3 cells/Liter
Standard Error 21211.91
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14lo+CD16br+, Week 1, n=5, 18
|
11248.2 10^3 cells/Liter
Standard Error 6598.36
|
4334.6 10^3 cells/Liter
Standard Error 3466.71
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14lo+CD16br+, Week 12, n=5, 21
|
10938.4 10^3 cells/Liter
Standard Error 5088.36
|
759.2 10^3 cells/Liter
Standard Error 2534.27
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14lo+CD16br+, 12-Week FU, n=5, 18
|
24737.0 10^3 cells/Liter
Standard Error 7758.65
|
3992.8 10^3 cells/Liter
Standard Error 4134.52
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14br+CD16-, Week 12, n=5, 21
|
-2981.8 10^3 cells/Liter
Standard Error 37788.70
|
13201.2 10^3 cells/Liter
Standard Error 18684.22
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14br+CD16-, 12-Week FU, n=5, 18
|
31906.6 10^3 cells/Liter
Standard Error 45766.70
|
-31512.8 10^3 cells/Liter
Standard Error 24027.16
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14lo+CD16br+, Week 4, n=6, 22
|
2522.9 10^3 cells/Liter
Standard Error 3757.96
|
291.3 10^3 cells/Liter
Standard Error 1959.54
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14-HLA-DR+CD11cbr+CD123-, Week 1, n=5, 18
|
-2017.6 10^3 cells/Liter
Standard Error 2452.91
|
738.7 10^3 cells/Liter
Standard Error 1266.25
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14-HLA-DR+CD11cbr+CD123-, Week 4, n=6, 22
|
2766.3 10^3 cells/Liter
Standard Error 3220.54
|
2278.8 10^3 cells/Liter
Standard Error 1696.12
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14-HLA-DR+CD11cbr+CD123-, Week 12, n=5, 21
|
5730.4 10^3 cells/Liter
Standard Error 5085.86
|
5453.0 10^3 cells/Liter
Standard Error 2399.11
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14-HLA-DR+CD11cbr+CD123-, 12-Week FU, n=5, 18
|
5785.6 10^3 cells/Liter
Standard Error 5081.59
|
5474.0 10^3 cells/Liter
Standard Error 2439.59
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14br+CD16+, Week 1, n=5, 18
|
-5376.0 10^3 cells/Liter
Standard Error 4748.95
|
1491.0 10^3 cells/Liter
Standard Error 2452.69
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14br+CD16+, Week 12, n=5, 21
|
25351.6 10^3 cells/Liter
Standard Error 9433.73
|
2668.0 10^3 cells/Liter
Standard Error 4589.28
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
CD14br+CD16-, Week 4, n=6, 22
|
-17173.8 10^3 cells/Liter
Standard Error 24181.15
|
10485.9 10^3 cells/Liter
Standard Error 12635.98
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)Population: ITT Population.
Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of CD14-CD16+CD66b+ cell. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for CD14-CD16+CD66b+ (10\^6/Liter) baseline value, treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+
Week 1, n=5, 19
|
-559.0 10^6 cells/Liter
Standard Error 269.84
|
-380.9 10^6 cells/Liter
Standard Error 137.31
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+
Week 4, n=6, 22
|
-581.9 10^6 cells/Liter
Standard Error 377.03
|
-41.5 10^6 cells/Liter
Standard Error 196.72
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+
Week 12, n=5, 21
|
-125.9 10^6 cells/Liter
Standard Error 460.53
|
-378.6 10^6 cells/Liter
Standard Error 229.47
|
|
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+
12-Week FU, n=5, 18
|
-240.9 10^6 cells/Liter
Standard Error 430.65
|
-199.3 10^6 cells/Liter
Standard Error 219.73
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)Population: ITT Population.
Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Complement biomarkers included analysis of Complement C3 and Complement C4. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C3, Week 2, n=8, 26
|
0.957 Ratio of complement biomarker
Geometric Coefficient of Variation 11.72
|
0.963 Ratio of complement biomarker
Geometric Coefficient of Variation 14.15
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C3, Week 4, n=9, 27
|
1.045 Ratio of complement biomarker
Geometric Coefficient of Variation 18.42
|
0.959 Ratio of complement biomarker
Geometric Coefficient of Variation 12.62
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C3, Week 6, n=7, 27
|
1.060 Ratio of complement biomarker
Geometric Coefficient of Variation 12.00
|
0.991 Ratio of complement biomarker
Geometric Coefficient of Variation 11.71
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C4, Week 6, n=7, 27
|
0.990 Ratio of complement biomarker
Geometric Coefficient of Variation 10.31
|
0.985 Ratio of complement biomarker
Geometric Coefficient of Variation 17.32
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C4, Week 12, n=7, 24
|
0.942 Ratio of complement biomarker
Geometric Coefficient of Variation 15.57
|
0.994 Ratio of complement biomarker
Geometric Coefficient of Variation 12.75
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C3, Week 1, n=9, 25
|
0.967 Ratio of complement biomarker
Geometric Coefficient of Variation 7.43
|
0.982 Ratio of complement biomarker
Geometric Coefficient of Variation 11.76
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C3, Week 8, n=7, 25
|
1.021 Ratio of complement biomarker
Geometric Coefficient of Variation 12.54
|
1.009 Ratio of complement biomarker
Geometric Coefficient of Variation 10.85
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C3, Week 12, n=7, 24
|
0.988 Ratio of complement biomarker
Geometric Coefficient of Variation 9.37
|
1.003 Ratio of complement biomarker
Geometric Coefficient of Variation 11.34
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C3, 12-Week FU, n=7, 22
|
1.005 Ratio of complement biomarker
Geometric Coefficient of Variation 19.15
|
0.995 Ratio of complement biomarker
Geometric Coefficient of Variation 10.65
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C4, Week 1, n=9, 25
|
1.005 Ratio of complement biomarker
Geometric Coefficient of Variation 11.40
|
0.969 Ratio of complement biomarker
Geometric Coefficient of Variation 13.13
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C4, Week 2, n=8, 26
|
0.949 Ratio of complement biomarker
Geometric Coefficient of Variation 9.64
|
0.984 Ratio of complement biomarker
Geometric Coefficient of Variation 16.45
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C4, Week 4, n=9, 27
|
0.999 Ratio of complement biomarker
Geometric Coefficient of Variation 12.06
|
0.945 Ratio of complement biomarker
Geometric Coefficient of Variation 14.63
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C4, Week 8, n=7, 25
|
0.979 Ratio of complement biomarker
Geometric Coefficient of Variation 7.66
|
1.006 Ratio of complement biomarker
Geometric Coefficient of Variation 13.53
|
|
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
Complement C4, 12-Week FU, n=7, 22
|
0.982 Ratio of complement biomarker
Geometric Coefficient of Variation 12.88
|
0.986 Ratio of complement biomarker
Geometric Coefficient of Variation 14.72
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)Population: ITT Population.
Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Complement biomarkers included analysis of Complement C4a, Complement C5a, Complement Split Factor SC5b-9 and Soluble CD163. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C4a, Week 2, n=8, 26
|
0.881 Ratio of complement biomarker
Geometric Coefficient of Variation 55.58
|
1.156 Ratio of complement biomarker
Geometric Coefficient of Variation 75.77
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C4a, Week 4, n=9, 27
|
0.840 Ratio of complement biomarker
Geometric Coefficient of Variation 40.85
|
1.100 Ratio of complement biomarker
Geometric Coefficient of Variation 46.87
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C4a, 12-Week FU, n=7, 21
|
1.104 Ratio of complement biomarker
Geometric Coefficient of Variation 40.27
|
1.221 Ratio of complement biomarker
Geometric Coefficient of Variation 56.53
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C5a, 12-Week FU, n=7, 22
|
1.152 Ratio of complement biomarker
Geometric Coefficient of Variation 42.75
|
1.130 Ratio of complement biomarker
Geometric Coefficient of Variation 32.16
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement Split Factor SC5b-9, Week 1, n=9, 27
|
0.971 Ratio of complement biomarker
Geometric Coefficient of Variation 37.46
|
1.020 Ratio of complement biomarker
Geometric Coefficient of Variation 43.70
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
sCD163, Week 4, n=9, 27
|
0.986 Ratio of complement biomarker
Geometric Coefficient of Variation 15.89
|
0.947 Ratio of complement biomarker
Geometric Coefficient of Variation 27.10
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
sCD163, Week 6, n=7, 27
|
0.938 Ratio of complement biomarker
Geometric Coefficient of Variation 20.83
|
0.959 Ratio of complement biomarker
Geometric Coefficient of Variation 30.14
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C4a, Week 1, n=9, 27
|
1.159 Ratio of complement biomarker
Geometric Coefficient of Variation 115.81
|
0.990 Ratio of complement biomarker
Geometric Coefficient of Variation 67.63
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C4a, Week 6, n=7, 27
|
0.914 Ratio of complement biomarker
Geometric Coefficient of Variation 66.71
|
0.860 Ratio of complement biomarker
Geometric Coefficient of Variation 53.87
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C4a, Week 8, n=7, 25
|
1.017 Ratio of complement biomarker
Geometric Coefficient of Variation 44.16
|
0.998 Ratio of complement biomarker
Geometric Coefficient of Variation 60.41
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C4a, Week 12, n=7, 24
|
0.927 Ratio of complement biomarker
Geometric Coefficient of Variation 58.05
|
0.901 Ratio of complement biomarker
Geometric Coefficient of Variation 93.48
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C5a, Week 1, n=9, 27
|
0.927 Ratio of complement biomarker
Geometric Coefficient of Variation 19.42
|
0.991 Ratio of complement biomarker
Geometric Coefficient of Variation 29.67
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C5a, Week 2, n=8, 26
|
1.154 Ratio of complement biomarker
Geometric Coefficient of Variation 36.82
|
1.015 Ratio of complement biomarker
Geometric Coefficient of Variation 55.60
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C5a, Week 4, n=9, 27
|
0.943 Ratio of complement biomarker
Geometric Coefficient of Variation 16.76
|
1.010 Ratio of complement biomarker
Geometric Coefficient of Variation 35.63
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C5a, Week 6, n=7, 27
|
1.139 Ratio of complement biomarker
Geometric Coefficient of Variation 61.77
|
1.044 Ratio of complement biomarker
Geometric Coefficient of Variation 33.94
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C5a, Week 8, n=7, 25
|
0.980 Ratio of complement biomarker
Geometric Coefficient of Variation 13.71
|
0.957 Ratio of complement biomarker
Geometric Coefficient of Variation 26.95
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement C5a, Week 12, n=7, 24
|
1.012 Ratio of complement biomarker
Geometric Coefficient of Variation 8.41
|
0.995 Ratio of complement biomarker
Geometric Coefficient of Variation 29.49
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement Split Factor SC5b-9, Week 2, n=8, 26
|
1.078 Ratio of complement biomarker
Geometric Coefficient of Variation 28.80
|
1.040 Ratio of complement biomarker
Geometric Coefficient of Variation 60.64
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement Split Factor SC5b-9, Week 4, n=9, 27
|
0.930 Ratio of complement biomarker
Geometric Coefficient of Variation 43.01
|
1.126 Ratio of complement biomarker
Geometric Coefficient of Variation 41.04
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement Split Factor SC5b-9, Week 6, n=7, 27
|
0.989 Ratio of complement biomarker
Geometric Coefficient of Variation 23.18
|
1.084 Ratio of complement biomarker
Geometric Coefficient of Variation 53.90
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement Split Factor SC5b-9, Week 8, n=7, 25
|
0.889 Ratio of complement biomarker
Geometric Coefficient of Variation 35.48
|
1.055 Ratio of complement biomarker
Geometric Coefficient of Variation 67.53
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement Split Factor SC5b-9, Week 12, n=7, 24
|
0.883 Ratio of complement biomarker
Geometric Coefficient of Variation 30.26
|
0.843 Ratio of complement biomarker
Geometric Coefficient of Variation 72.14
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
Complement Split Factor SC5b-9,12-Week FU, n=7, 22
|
1.039 Ratio of complement biomarker
Geometric Coefficient of Variation 69.05
|
1.041 Ratio of complement biomarker
Geometric Coefficient of Variation 38.60
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
sCD163, Week 1, n=9, 27
|
0.993 Ratio of complement biomarker
Geometric Coefficient of Variation 24.28
|
0.963 Ratio of complement biomarker
Geometric Coefficient of Variation 16.38
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
sCD163, Week 2, n=8, 26
|
1.101 Ratio of complement biomarker
Geometric Coefficient of Variation 17.80
|
0.954 Ratio of complement biomarker
Geometric Coefficient of Variation 17.14
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
sCD163, Week 8, n=7, 25
|
0.938 Ratio of complement biomarker
Geometric Coefficient of Variation 30.03
|
0.950 Ratio of complement biomarker
Geometric Coefficient of Variation 28.73
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
sCD163, Week 12, n=7, 24
|
0.937 Ratio of complement biomarker
Geometric Coefficient of Variation 24.86
|
0.915 Ratio of complement biomarker
Geometric Coefficient of Variation 35.29
|
|
Change From Baseline in Complement Biomarkers: Complement Component 4a (C4a), Complement Component 5a (C5a), Complement Split Factor SC5b-9, Soluble Cluster of Differentiation 163 (sCD163)
sCD163, 12-Week FU, n=7, 21
|
1.200 Ratio of complement biomarker
Geometric Coefficient of Variation 32.94
|
0.994 Ratio of complement biomarker
Geometric Coefficient of Variation 28.84
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)Population: ITT Population.
Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Mechanistic biomarkers included analysis of Interleukin 1 Beta, Interleukin 10, Interleukin 15, Interleukin 17 Alpha, Interleukin 17F, Interleukin 8 and Tumor Necrosis Factor. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. NA indicates that data is not available since 100% of the data was below limit of quantification at all time points. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 15, 12-Week FU, n=7, 21
|
0.871 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 37.95
|
0.636 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 111.86
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17 Alpha, Week 2, n=8, 25
|
0.935 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 75.58
|
0.942 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 72.24
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17 Alpha, Week 6, n=7, 26
|
1.015 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 76.60
|
0.867 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 90.15
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17 Alpha, Week 8, n=7, 23
|
0.905 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 77.24
|
1.005 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 135.76
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17F, Week 6, n=7, 25
|
0.787 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 32.55
|
1.013 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 107.49
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 8, Week 2, n=8, 26
|
1.505 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 43.78
|
0.861 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 78.64
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 8, Week 4, n=9, 27
|
1.102 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 38.30
|
0.773 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 82.48
|
|
Change From Baseline in Mechanistic Biomarkers
Tumor Necrosis Factor,12-Week FU, n=7, 21
|
1.619 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 180.16
|
1.057 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 34.72
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 15, Week 1, n=9, 27
|
1.001 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 12.70
|
0.950 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 59.23
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 15, Week 2, n=8, 26
|
0.882 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 41.99
|
0.849 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 102.76
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 15, Week 4, n=9, 27
|
1.206 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 47.87
|
0.831 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 84.07
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 1 Beta, Week 1, n=9, 26
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 1 Beta, Week 2, n=8, 26
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 1 Beta, Week 4, n=9, 27
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 1 Beta, Week 6, n=7, 27
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 1 Beta, Week 8, n=7, 25
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 1 Beta, Week 12, n=7, 24
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 1 Beta, 12-Week FU, n=7, 21
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
1.000 Ratio of mechanistic biomarker
Geometric Coefficient of Variation NA
100% of data was below limit of quantification at all time points, hence no variability.
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 10, Week 1, n=9, 26
|
0.962 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 11.55
|
0.994 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 28.47
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 10, Week 2, n=8, 26
|
1.206 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 45.35
|
1.048 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 37.27
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 10, Week 4, n=9, 27
|
0.875 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 41.69
|
0.985 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 32.52
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 10, Week 6, n=7, 27
|
0.842 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 47.84
|
0.960 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 17.66
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 10, Week 8, n=7, 25
|
1.197 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 50.41
|
0.969 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 30.23
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 10, Week 12, n=7, 24
|
0.842 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 47.84
|
0.989 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 21.36
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 10, 12-Week FU, n=7, 21
|
0.842 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 47.84
|
1.230 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 62.91
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 15, Week 6, n=7, 27
|
1.297 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 48.81
|
0.904 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 90.53
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 15, Week 8, n=7, 25
|
0.871 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 37.95
|
0.865 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 90.30
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 15, Week 12, n=7, 24
|
0.871 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 37.95
|
0.771 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 82.21
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 8, 12-Week FU, n=7, 21
|
1.191 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 42.58
|
0.841 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 96.92
|
|
Change From Baseline in Mechanistic Biomarkers
Tumor Necrosis Factor, Week 1, n=9, 26
|
0.976 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 15.20
|
0.994 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 18.45
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17 Alpha, Week 1, n=9, 25
|
0.806 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 53.03
|
1.054 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 93.04
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17 Alpha, Week 4, n=9, 26
|
0.995 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 91.45
|
0.911 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 102.66
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17 Alpha, Week 12, n=7, 23
|
1.007 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 87.84
|
0.857 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 101.45
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17 Alpha, 12-Week FU, n=7, 20
|
0.969 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 155.67
|
0.999 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 150.12
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17F, Week 1, n=9, 25
|
1.153 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 36.21
|
0.797 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 78.96
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17F, Week 2, n=8, 26
|
1.062 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 74.38
|
0.911 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 72.36
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17F, Week 4, n=9, 26
|
0.966 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 21.09
|
0.948 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 89.47
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17F, Week 8, n=7, 25
|
0.947 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 19.20
|
0.815 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 91.93
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17F, Week 12, n=7, 23
|
1.002 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 74.09
|
0.884 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 100.03
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 17F, 12-Week FU, n=7, 21
|
1.130 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 101.51
|
0.741 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 90.62
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 8, Week 1, n=9, 26
|
1.104 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 40.98
|
1.081 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 74.78
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 8, Week 6, n=7, 27
|
1.229 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 61.82
|
0.720 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 72.70
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 8, Week 8, n=7, 25
|
1.547 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 53.88
|
0.761 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 80.51
|
|
Change From Baseline in Mechanistic Biomarkers
Interleukin 8, Week 12, n=7, 24
|
1.240 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 49.03
|
0.850 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 80.98
|
|
Change From Baseline in Mechanistic Biomarkers
Tumor Necrosis Factor, Week 2, n=8, 26
|
0.951 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 19.84
|
0.977 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 16.81
|
|
Change From Baseline in Mechanistic Biomarkers
Tumor Necrosis Factor, Week 4, n=9, 27
|
0.933 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 17.70
|
0.871 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 48.19
|
|
Change From Baseline in Mechanistic Biomarkers
Tumor Necrosis Factor, Week 6, n=7, 27
|
1.087 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 36.81
|
0.929 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 21.48
|
|
Change From Baseline in Mechanistic Biomarkers
Tumor Necrosis Factor, Week 8, n=7, 25
|
1.110 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 25.33
|
0.930 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 20.85
|
|
Change From Baseline in Mechanistic Biomarkers
Tumor Necrosis Factor, Week 12, n=7, 24
|
1.021 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 38.53
|
0.969 Ratio of mechanistic biomarker
Geometric Coefficient of Variation 29.74
|
PRIMARY outcome
Timeframe: Baseline and Week 12, 12-Week FU (Week 22)Population: ITT Population.
Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Safety biomarkers included analysis of 3B-Cholestenoic Acid and Surfactant Protein D. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D
3B-Cholestenoic Acid, Week 12, n=7, 24
|
1.012 Ratio of safety biomarker
Geometric Coefficient of Variation 16.52
|
1.094 Ratio of safety biomarker
Geometric Coefficient of Variation 19.45
|
|
Change From Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D
3B-Cholestenoic Acid, Week 22, n=7, 22
|
1.020 Ratio of safety biomarker
Geometric Coefficient of Variation 20.25
|
1.009 Ratio of safety biomarker
Geometric Coefficient of Variation 22.67
|
|
Change From Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D
Surfactant Protein D, Week 12, n=7, 24
|
1.003 Ratio of safety biomarker
Geometric Coefficient of Variation 23.10
|
1.134 Ratio of safety biomarker
Geometric Coefficient of Variation 27.96
|
|
Change From Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D
Surfactant Protein D, 12-Week FU, n=7, 21
|
1.140 Ratio of safety biomarker
Geometric Coefficient of Variation 45.71
|
0.985 Ratio of safety biomarker
Geometric Coefficient of Variation 31.32
|
PRIMARY outcome
Timeframe: Baseline and Week 12, 12-Week FU (Week 22)Population: ITT Population.
Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Safety biomarker included analysis of KL-6 Antigen. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Safety Biomarkers: KL-6 Antigen
Week 12, n=6, 24
|
1.416 Ratio of safety biomarker
Geometric Coefficient of Variation 220.58
|
1.099 Ratio of safety biomarker
Geometric Coefficient of Variation 66.17
|
|
Change From Baseline in Safety Biomarkers: KL-6 Antigen
12-Week FU, n=6, 21
|
0.937 Ratio of safety biomarker
Geometric Coefficient of Variation 62.43
|
1.024 Ratio of safety biomarker
Geometric Coefficient of Variation 93.56
|
SECONDARY outcome
Timeframe: Up to 12-Week FU (Week 22)Population: ITT Population
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect and associated with liver injury and impaired liver function. An AESI include serious infections, opportunistic infections, neutropenia, respiratory events, pulmonary alveolar proteinosis, hypersensitivity reactions, injection site reactions, persistent cough or dyspnea.
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)
Any SAEs
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)
Any AEs
|
4 Participants
|
11 Participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)
AESI
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 12-Week FU (Week 22)Population: Immunogenicity Population
Immunogenicity samples for determination of anti-drug-antibody (ADA) were collected. The presence of treatment emergent ADA was determined using a GSK3196165 bridging style ADA assay with a bio-analytically determined cut point determined during assay validation. Samples taken after dosing with GSK3196165 that had a value at or above the cut-point was considered potentially treatment-emergent ADA-positive. The immunogenicity population consisted of all participants in the ITT population, who had at least one valid immunogenicity assessment.
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Number of Participants Who Tested Positive for Anti-GSK3196165 Binding Antibody Detection at Any Time Post-Baseline
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, 12-Week FU (Week 22)Population: ITT Population.
For synovitis a total of 8 joints were evaluated. Individual joint scores range from 0-3, where 0= normal, 1=mild, 2=moderate and 3=severe. The final synovitis score is the sum of the individual joint scores. Total score range from 0 (best) to 24 (worst). If an individual location is scored either 'Not Visible' or 'Surgically Modified' then the score for that location was set to missing. Missing joint scores was imputed as the mean of the non-missing joint scores. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Repeated measures analysis adjusted for synovitis score baseline value, treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Data has been presented for Median and 95% credible interval. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Synovitis as Assessed by Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) in the Most Affected Hand/Wrist
12-Week FU, n=7, 19
|
1.13 Scores on a scale
Interval -1.32 to 3.55
|
-1.13 Scores on a scale
Interval -2.47 to 0.2
|
|
Change From Baseline in Synovitis as Assessed by Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) in the Most Affected Hand/Wrist
Week 4, n=6, 12
|
0.05 Scores on a scale
Interval -1.92 to 1.95
|
-0.07 Scores on a scale
Interval -1.19 to 1.12
|
|
Change From Baseline in Synovitis as Assessed by Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) in the Most Affected Hand/Wrist
Week 12, n=5, 21
|
0.84 Scores on a scale
Interval -1.57 to 3.12
|
-1.33 Scores on a scale
Interval -2.54 to -0.13
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, 12-Week FU (Week 22)Population: ITT Population.
For bone edema/osteitis a total of 25 locations was evaluated. Individual location scores ranged from 0-3, where, 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100% of bone edematous. Final bone edema/osteitis score is sum of individual location scores. Total score ranged from 0 (best) to 75 (worst). Baseline was defined at Day 1. Change from Baseline was calculated by subtracting post-dose value from Baseline value. If an individual location was scored either 'Not Visible' or 'Surgically Modified' or 'Not Assessable' then the score for that location was set to be missing. Missing joint scores was imputed as mean of non-missing location scores. Repeated measures analysis adjusted for Bone Edema/Osteitis Score baseline value, treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Osteitis as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist
Week 4, n=6, 12
|
-0.1 Scores on a scale
Standard Error 0.11
|
-0.1 Scores on a scale
Standard Error 0.06
|
|
Change From Baseline in Osteitis as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist
Week 12, n=5, 21
|
0.0 Scores on a scale
Standard Error 1.04
|
-0.8 Scores on a scale
Standard Error 0.56
|
|
Change From Baseline in Osteitis as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist
12-Week FU, n=7,19
|
0.5 Scores on a scale
Standard Error 1.33
|
-0.9 Scores on a scale
Standard Error 0.74
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, 12-Week FU (Week 22)Population: ITT Population.
For bone erosion a total of 25 locations were evaluated. Individual location scores range from 0-10, where, 0: no erosion; 1: 1-10% of bone eroded and 10: 91-100% of bone eroded. The final bone erosion score is the sum of the individual location scores. The total score ranged from 0 (best) to 250 (worst). If an individual location was scored either 'Not Visible' or 'Surgically Modified' or 'Not Assessable' then the score for that location was set to be missing. Missing joint scores was imputed as the mean of the non-missing location scores. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for Bone Erosion Score baseline value, treatment group, disease duration (\<=2 or \>2 years), visit and treatment group. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles.
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Erosion as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist
Week 4, n=6, 12
|
0.2 Scores on a scale
Standard Error 0.49
|
0.3 Scores on a scale
Standard Error 0.30
|
|
Change From Baseline in Erosion as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist
Week 12, n=5, 21
|
0.8 Scores on a scale
Standard Error 0.50
|
0.4 Scores on a scale
Standard Error 0.26
|
|
Change From Baseline in Erosion as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist
12-Week FU, n=7, 19
|
1.5 Scores on a scale
Standard Error 0.47
|
0.5 Scores on a scale
Standard Error 0.27
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12 and 12-Week FU (Week 22)Population: ITT Population.
RAMRIQ is an automated volume quantification assessment. RAMRIQ assessed same pathologies and joints (except metacarpophalangeal joint \[MCP1\]) as RAMRIS allowing for direct comparison of results obtained using the two methods. Bones were automatically identified in pre-contrast, coronal T1 images using active appearance modelling (AAMs). Joint capsules and soft tissues were also segmented with AAMs, providing consistent 3D regions of interest (ROI) for synovial enhancement across all time points. Synovial volume was calculated as voxels that enhance within each ROI. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Repeated measures analysis adjusted for Synovitis baseline value, treatment group, disease duration (\<=2 or \>2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Synovitis as Assessed by Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Assessment in the Most Affected Hand/Wrist
Week 4, n=6, 12
|
34.1 Milliliters
Standard Error 1052.52
|
245.5 Milliliters
Standard Error 776.24
|
|
Change From Baseline in Synovitis as Assessed by Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Assessment in the Most Affected Hand/Wrist
Week 12, n=5, 21
|
-912.3 Milliliters
Standard Error 1405.77
|
-1417.0 Milliliters
Standard Error 671.54
|
|
Change From Baseline in Synovitis as Assessed by Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Assessment in the Most Affected Hand/Wrist
12-Week FU, n=7, 19
|
364.0 Milliliters
Standard Error 1372.20
|
-1172.1 Milliliters
Standard Error 844.13
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12 and 12-Week FU (Week 22)Population: ITT Population.
RAMRIQ is an automated volume quantification assessment for edema volume. RAMRIQ assessed the same pathologies and joints (except MCP1) as RAMRIS, allowing for direct comparison of results obtained using the two methods. Bones were automatically identified in pre-contrast, coronal T1 images using AAMs. Joint capsules and soft tissues were also segmented with AAMs, providing consistent 3D ROI for synovial enhancement across all time points. Edema volume was defined as non-erosion contrast-enhancing voxels inside the bone. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Osteitis as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist
Week 12, n=5, 21
|
-0.0045 Milliliters
Standard Error 0.0035
|
-0.0009 Milliliters
Standard Error 0.0019
|
|
Change From Baseline in Osteitis as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist
Week 4, n=6, 12
|
-0.0045 Milliliters
Standard Error 0.0102
|
0.0084 Milliliters
Standard Error 0.0057
|
|
Change From Baseline in Osteitis as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist
12-Week FU, n=7, 19
|
-0.0038 Milliliters
Standard Error 0.0016
|
-0.0027 Milliliters
Standard Error 0.0009
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12 and 12-Week FU (Week 22)Population: ITT Population.
RAMRIQ is an automated volume quantification assessment for erosion volume. RAMRIQ assessed the same pathologies and joints (except MCP1) as RAMRIS, allowing for direct comparison of results obtained using the two methods. Bones were automatically identified in pre-contrast, coronal T1 images using AAMs. Joint capsules and soft tissues were also segmented with AAMs, providing consistent 3D ROI for synovial enhancement across all time points. Erosion volume was identified inside the bone surfaces using voxel-based classification. The volume of BME and erosions was normalised to total bone volume for statistical analysis. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Outcome measures
| Measure |
Placebo
n=11 Participants
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 Participants
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Change From Baseline in Erosion as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist
Week 4, n=6, 12
|
0.0007 Milliliters
Standard Error 0.0012
|
0.0006 Milliliters
Standard Error 0.0008
|
|
Change From Baseline in Erosion as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist
Week 12, n=5, 21
|
0.0003 Milliliters
Standard Error 0.0011
|
-0.0000 Milliliters
Standard Error 0.0006
|
|
Change From Baseline in Erosion as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist
12-Week FU, n=7, 19
|
-0.0002 Milliliters
Standard Error 0.0023
|
0.0003 Milliliters
Standard Error 0.0013
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
GSK3196165 180 mg
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=11 participants at risk
Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5-25 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
GSK3196165 180 mg
n=28 participants at risk
Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5-5 mg/week and folic (or folinic) acid \>=5 mg/week during the combination treatment period.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
18.2%
2/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
0.00%
0/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
18.2%
2/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
0.00%
0/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Infections and infestations
Upper respiratory tract infection
|
9.1%
1/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Infections and infestations
Laryngitis
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
7.1%
2/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
9.1%
1/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
0.00%
0/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Skin and subcutaneous tissue disorders
Rosacea
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Cardiac disorders
Coronary artery disease
|
9.1%
1/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
0.00%
0/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
General disorders
Fatigue
|
9.1%
1/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
0.00%
0/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Investigations
Weight increased
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Nervous system disorders
Headache
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
|
Psychiatric disorders
Initial insomnia
|
0.00%
0/11 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
3.6%
1/28 • AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22).
ITT Population was used for the analysis of safety data.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER