Arthritis, Rheumatoid
Conditions
Keywords
GSK3196165, magnetic resonance imaging (MRI), disease-modifying antirheumatic drugs (DMARDs), granulocyte-macrophage colony stimulating factor (GM-CSF), Rheumatoid Arthritis, Methotrexate
Brief summary
This study is designed to explore the activity of granulocyte-macrophage colony stimulating factor (GM-CSF) signaling pathway in subjects with rheumatoid arthritis (RA), the potential impact of inhibition of this axis by GSK3196165, and to evaluate whether there are any differences in the GM-CSF axis between subjects with early RA compared with those with more established disease. This study also aims to establish the potential impact of GSK3196165 on inflammatory structural joint damage in the hand/wrist using magnetic resonance imaging (MRI). This is a randomized Phase IIa, multi-center, double-blind, placebo-controlled parallel group study. Approximately 40 subjects with active RA despite treatment with disease-modifying antirheumatic drugs (DMARDs) (including conventional or biologic) will be randomized into the study, following a screening period of up to 6 weeks. The total treatment period is up to 10 weeks, with a 12-week follow-up period after the last dose (Week 22).
Interventions
DRUGGSK3196165
GSK3196165 is supplied as liquid and will be administered as SC injection.
DRUGPlacebo
0.9% weight by volume (w/v) sodium chloride solution administered as SC injection.
DRUGMTX
Capsule, tablet or liquid administered orally or as SC injection.
DRUGFolic (or folinic) acid
Capsule, tablet or liquid and will be administered orally.
Sponsors
Parexel
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>=18 years at the time of signing informed consent. * Meets American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 RA Classification Criteria AND subject not diagnosed before age of 16 years. * Functional class I, II or III defined by the 1992 ACR Classification of Functional Status in RA. * Active disease as defined by: * Swollen joint count of \>=4 (66-joint count) and tender joint count of \>=4 (68-joint count) at screening and Day 1. AND • Disease activity score for 28 different joints with C-reactive protein (CRP) value (DAS28\[CRP\]) \>=3.2 at screening. AND • CRP \>=3.0 milligrams (mg)/liter (L). * Signs of inflammation such as synovitis in the MRI scan of the most-affected hand. * Must be currently taking MTX (15-25 mg weekly) (oral/injected) for at least 12 weeks before screening, with no change in route of administration, with a stable and tolerated dose for \>=4 weeks prior to Day 1. A stable dose of MTX \>=7.5 mg/week is acceptable, if the MTX dose has been reduced for reasons of documented intolerance to MTX, example (e.g.) hepatic or hematologic toxicity, or per local requirement. * Body weight \>=45 kilograms (kg). * Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria. * Capable of giving signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the consent form and in the protocol. * Willing to continue or initiate treatment with oral folic acid (at least 5 mg/week) or equivalent and be treated during the entire study (mandatory co-medication for MTX treatment). * Diffusing capacity of the lung for carbon monoxide (DLCO) \>=60% predicted; forced expiratory volume in 1 second (FEV1) \>=70% predicted. * No evidence of active or latent infection with Mycobacterium tuberculosis (TB).
Exclusion criteria
* Pregnant or lactating, or women planning to become pregnant or initiating breastfeeding. * History of other inflammatory rheumatologic or autoimmune disorders, other than Sjögren's syndrome secondary to RA. * History of any respiratory disease which (in the opinion of the investigator) would compromise subject safety or the ability of the subject to complete the study (e.g. significant interstitial lung disease, such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), moderate-severe asthma, bronchiectasis, previous pulmonary alveolar proteinosis \[PAP\]). * Clinically-significant (in the opinion of the investigator) persistent cough or clinically significant or unstable dyspnea that is unexplained. * Significant unstable or uncontrolled acute or chronic disease which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk. * A history of malignancy. * Contraindication to MRI scanning. * Current/previous Hepatitis B virus (HBV), Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) 1 or 2 infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Safety Biomarkers: KL-6 Antigen | Baseline and Week 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127- | Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in T Helper Cell Panel Events | Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+ | Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+ | Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22) | 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). |
| 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) | Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Mechanistic Biomarkers | Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D | Baseline and Week 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Target Engagement Biomarkers- Soluble Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) Complexed to GSK3196165 | Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week follow-up (FU) (Week 22) | 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). |
| Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9 | Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Predictive Biomarkers: Amyloid A | Baseline and Week 12, 12-Week FU (Week 22) | 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. |
| 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 | Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22) | 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. |
| Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Cartilage Biomarkers | Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Flow Cytometry: Helper/Suppressor Cells | Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+ | Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL) | Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+ | Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Tested Positive for Anti-GSK3196165 Binding Antibody Detection at Any Time Post-Baseline | Up to 12-Week FU (Week 22) | 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. |
| 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 | Baseline and Weeks 4, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Osteitis as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist | Baseline and Weeks 4, 12, 12-Week FU (Week 22) | 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). |
| Change From Baseline in Erosion as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist | Baseline and Weeks 4, 12, 12-Week FU (Week 22) | 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. |
| Change From Baseline in Synovitis as Assessed by Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Assessment in the Most Affected Hand/Wrist | Baseline and Weeks 4, 12 and 12-Week FU (Week 22) | 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). |
| Change From Baseline in Osteitis as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist | Baseline and Weeks 4, 12 and 12-Week FU (Week 22) | 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). |
| Change From Baseline in Erosion as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist | Baseline and Weeks 4, 12 and 12-Week FU (Week 22) | 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). |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Up to 12-Week FU (Week 22) | 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. |
Countries
Germany, Poland, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 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. | 11 |
| GSK3196165 180 mg 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. | 28 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | GSK3196165 180 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 59.1 Years STANDARD_DEVIATION 9.47 | 56.6 Years STANDARD_DEVIATION 10.73 | 50.3 Years STANDARD_DEVIATION 11.57 |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 6 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 24 Participants | 33 Participants | 9 Participants |
| Sex: Female, Male Female | 24 Participants | 34 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 28 |
| other Total, other adverse events | 4 / 11 | 11 / 28 |
| serious Total, serious adverse events | 0 / 11 | 0 / 28 |
Outcome results
Primary
Change From Baseline in Cartilage Biomarkers
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).
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Cartilage Biomarkers | MD3C, Week 4, n=9, 27 | 0.940 Ratio of cartilage biomarker | Geometric Coefficient of Variation 8.06 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD3C, Week 6, n=7, 27 | 1.013 Ratio of cartilage biomarker | Geometric Coefficient of Variation 8.09 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD3C, Week 8, n=7, 25 | 0.918 Ratio of cartilage biomarker | Geometric Coefficient of Variation 9.04 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD3C, Week 12, n=7, 24 | 0.929 Ratio of cartilage biomarker | Geometric Coefficient of Variation 9.28 |
| Placebo | 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 |
| Placebo | Change From Baseline in Cartilage Biomarkers | ARGS Neo-Epitope, Week 1, n=9, 27 | 0.979 Ratio of cartilage biomarker | Geometric Coefficient of Variation 16.1 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Change From Baseline in Cartilage Biomarkers | CMDV, Week 1,n=9,27 | 0.981 Ratio of cartilage biomarker | Geometric Coefficient of Variation 24.12 |
| Placebo | Change From Baseline in Cartilage Biomarkers | CMDV,Week 2,n=8,26 | 0.820 Ratio of cartilage biomarker | Geometric Coefficient of Variation 28.46 |
| Placebo | Change From Baseline in Cartilage Biomarkers | CMDV, Week 4,n=9,27 | 0.715 Ratio of cartilage biomarker | Geometric Coefficient of Variation 27.3 |
| Placebo | Change From Baseline in Cartilage Biomarkers | CMDV, Week 6,n=7,27 | 1.099 Ratio of cartilage biomarker | Geometric Coefficient of Variation 30.47 |
| Placebo | Change From Baseline in Cartilage Biomarkers | CMDV, Week 8,n=7,25 | 0.929 Ratio of cartilage biomarker | Geometric Coefficient of Variation 24.72 |
| Placebo | Change From Baseline in Cartilage Biomarkers | CMDV, Week12,n=7,24 | 1.123 Ratio of cartilage biomarker | Geometric Coefficient of Variation 29.34 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD1C, Week 1, n=9, 27 | 1.079 Ratio of cartilage biomarker | Geometric Coefficient of Variation 9.6 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD1C, Week 2, n=8, 26 | 1.028 Ratio of cartilage biomarker | Geometric Coefficient of Variation 11.98 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD1C, Week 4, n=9, 27 | 1.142 Ratio of cartilage biomarker | Geometric Coefficient of Variation 14.57 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD1C, Week 6, n=7, 27 | 1.392 Ratio of cartilage biomarker | Geometric Coefficient of Variation 12.64 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD1C, Week 8, n=7, 25 | 1.131 Ratio of cartilage biomarker | Geometric Coefficient of Variation 13.05 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD1C, Week 12, n=7, 24 | 1.148 Ratio of cartilage biomarker | Geometric Coefficient of Variation 13.74 |
| Placebo | 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 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD2C, Week 1, n=9, 27 | 1.059 Ratio of cartilage biomarker | Geometric Coefficient of Variation 11.83 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD2C, Week 2, n=8, 26 | 1.046 Ratio of cartilage biomarker | Geometric Coefficient of Variation 11.27 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD2C, Week 4, n=9, 27 | 1.035 Ratio of cartilage biomarker | Geometric Coefficient of Variation 10.18 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD2C, Week 6, n=7, 27 | 1.158 Ratio of cartilage biomarker | Geometric Coefficient of Variation 12.07 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD2C, Week 8, n=7, 25 | 1.091 Ratio of cartilage biomarker | Geometric Coefficient of Variation 11.42 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD2C, Week 12, n=7, 24 | 1.174 Ratio of cartilage biomarker | Geometric Coefficient of Variation 10.73 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD2C, 12-Week FU, n=7, 21 | 1.338 Ratio of cartilage biomarker | Geometric Coefficient of Variation 13.1 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD3C, Week 1, n=9, 27 | 0.950 Ratio of cartilage biomarker | Geometric Coefficient of Variation 6.44 |
| Placebo | Change From Baseline in Cartilage Biomarkers | MD3C, Week 2, n=8, 26 | 0.920 Ratio of cartilage biomarker | Geometric Coefficient of Variation 6.82 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MMP-Degraded CRP, Week 2, n=8, 26 | 1.000 Ratio of cartilage biomarker | Geometric Coefficient of Variation 3.07 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD3C, Week 4, n=9, 27 | 0.886 Ratio of cartilage biomarker | Geometric Coefficient of Variation 4.68 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD3C, Week 1, n=9, 27 | 0.959 Ratio of cartilage biomarker | Geometric Coefficient of Variation 3.74 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD3C, Week 6, n=7, 27 | 0.894 Ratio of cartilage biomarker | Geometric Coefficient of Variation 4.34 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MMP-Degraded CRP, Week 4, n=9, 27 | 1.004 Ratio of cartilage biomarker | Geometric Coefficient of Variation 3.49 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD3C, Week 8, n=7, 25 | 0.881 Ratio of cartilage biomarker | Geometric Coefficient of Variation 4.84 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD1C, Week 12, n=7, 24 | 1.023 Ratio of cartilage biomarker | Geometric Coefficient of Variation 7.81 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD3C, Week 12, n=7, 24 | 0.910 Ratio of cartilage biomarker | Geometric Coefficient of Variation 5.08 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MMP-Degraded CRP, Week 6, n=7, 27 | 1.099 Ratio of cartilage biomarker | Geometric Coefficient of Variation 3.5 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD3C, 12-Week FU, n=7, 21 | 0.910 Ratio of cartilage biomarker | Geometric Coefficient of Variation 5.46 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD2C, Week 12, n=7, 24 | 1.072 Ratio of cartilage biomarker | Geometric Coefficient of Variation 5.87 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | CMDV, Week 1,n=9,27 | 0.876 Ratio of cartilage biomarker | Geometric Coefficient of Variation 13.8 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD2C, Week 6, n=7, 27 | 1.064 Ratio of cartilage biomarker | Geometric Coefficient of Variation 6.3 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | ARGS Neo-Epitope, Week 1, n=9, 27 | 1.075 Ratio of cartilage biomarker | Geometric Coefficient of Variation 9.67 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MMP-Degraded CRP, Week 8, n=7, 25 | 1.087 Ratio of cartilage biomarker | Geometric Coefficient of Variation 4.05 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | ARGS Neo-Epitope, Week 2, n=8, 25 | 1.249 Ratio of cartilage biomarker | Geometric Coefficient of Variation 9.87 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD1C, 12-Week FU, n=7, 21 | 0.952 Ratio of cartilage biomarker | Geometric Coefficient of Variation 8.31 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | ARGS Neo-Epitope, Week 4, n=8, 26 | 1.104 Ratio of cartilage biomarker | Geometric Coefficient of Variation 10.05 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MMP-Degraded CRP, Week 12, n=7, 24 | 1.108 Ratio of cartilage biomarker | Geometric Coefficient of Variation 3.95 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | ARGS Neo-Epitope, Week 6, n=6, 26 | 1.164 Ratio of cartilage biomarker | Geometric Coefficient of Variation 7.82 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD2C, 12-Week FU, n=7, 21 | 1.041 Ratio of cartilage biomarker | Geometric Coefficient of Variation 7.5 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | ARGS Neo-Epitope, Week 8, n=7, 24 | 1.238 Ratio of cartilage biomarker | Geometric Coefficient of Variation 14.2 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MMP-Degraded CRP, 12-Week FU, n=7, 21 | 1.129 Ratio of cartilage biomarker | Geometric Coefficient of Variation 4.48 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | ARGS Neo-Epitope, Week 12, n=7, 24 | 1.156 Ratio of cartilage biomarker | Geometric Coefficient of Variation 7.78 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD2C, Week 1, n=9, 27 | 1.038 Ratio of cartilage biomarker | Geometric Coefficient of Variation 6.88 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | ARGS Neo-Epitope, 12-Week FU, n=8, 21 | 1.124 Ratio of cartilage biomarker | Geometric Coefficient of Variation 9.86 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD1C, Week 1, n=9, 27 | 0.858 Ratio of cartilage biomarker | Geometric Coefficient of Variation 5.63 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD2C, Week 8, n=7, 25 | 1.023 Ratio of cartilage biomarker | Geometric Coefficient of Variation 6.12 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | CMDV,Week 2,n=8,26 | 0.714 Ratio of cartilage biomarker | Geometric Coefficient of Variation 15.89 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD1C, Week 2, n=8, 26 | 0.907 Ratio of cartilage biomarker | Geometric Coefficient of Variation 6.63 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | CMDV, Week 4,n=9,27 | 0.801 Ratio of cartilage biomarker | Geometric Coefficient of Variation 15.52 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD2C, Week 2, n=8, 26 | 1.015 Ratio of cartilage biomarker | Geometric Coefficient of Variation 6.28 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | CMDV, Week 6,n=7,27 | 0.726 Ratio of cartilage biomarker | Geometric Coefficient of Variation 15.94 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD1C, Week 4, n=9, 27 | 0.896 Ratio of cartilage biomarker | Geometric Coefficient of Variation 8.35 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | CMDV, Week 8,n=7,25 | 0.759 Ratio of cartilage biomarker | Geometric Coefficient of Variation 13.39 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD3C, Week 2, n=8, 26 | 0.954 Ratio of cartilage biomarker | Geometric Coefficient of Variation 3.91 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | CMDV, Week12,n=7,24 | 0.917 Ratio of cartilage biomarker | Geometric Coefficient of Variation 16 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD1C, Week 6, n=7, 27 | 0.889 Ratio of cartilage biomarker | Geometric Coefficient of Variation 6.98 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | CMDV, 12-Week FU,n=7,21 | 0.769 Ratio of cartilage biomarker | Geometric Coefficient of Variation 15.81 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD2C, Week 4, n=9, 27 | 1.003 Ratio of cartilage biomarker | Geometric Coefficient of Variation 5.86 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MMP-Degraded CRP, Week 1, n=9, 27 | 1.021 Ratio of cartilage biomarker | Geometric Coefficient of Variation 3.99 |
| GSK3196165 180 mg | Change From Baseline in Cartilage Biomarkers | MD1C, Week 8, n=7, 25 | 0.904 Ratio of cartilage biomarker | Geometric Coefficient of Variation 7.23 |
Comparison: ARGS Neo-Epitope, Week 1p-value: 0.62195% CI: [0.75, 1.606]Repeated measures analysis
Comparison: ARGS Neo-Epitope, Week 2p-value: 0.03195% CI: [1.046, 2.388]Repeated measures analysis
Comparison: ARGS Neo-Epitope, Week 4p-value: 0.31795% CI: [0.817, 1.827]Repeated measures analysis
Comparison: ARGS Neo-Epitope, Week 6p-value: 0.11395% CI: [0.936, 1.81]Repeated measures analysis
Comparison: ARGS Neo-Epitope, Week 8p-value: 0.21795% CI: [0.795, 2.645]Repeated measures analysis
Comparison: ARGS Neo-Epitope, Week 12p-value: 0.14795% CI: [0.916, 1.75]Repeated measures analysis
Comparison: ARGS Neo-Epitope, 12-Week FUp-value: 0.98595% CI: [0.662, 1.499]Repeated measures analysis
Comparison: CMDV, Week 1p-value: 0.68195% CI: [0.511, 1.56]Repeated measures analysis
Comparison: CMDV, Week 2p-value: 0.66895% CI: [0.454, 1.669]Repeated measures analysis
Comparison: CMDV, Week 4p-value: 0.71795% CI: [0.597, 2.101]Repeated measures analysis
Comparison: CMDV, Week 6p-value: 0.22795% CI: [0.333, 1.31]Repeated measures analysis
Comparison: CMDV, Week 8p-value: 0.47195% CI: [0.464, 1.437]Repeated measures analysis
Comparison: CMDV, Week 12p-value: 0.54195% CI: [0.417, 1.597]Repeated measures analysis
Comparison: CMDV, 12-Week FUp-value: 0.54495% CI: [0.422, 1.602]Repeated measures analysis
Comparison: MMP-Degraded CRP, Week 1p-value: 0.53795% CI: [0.895, 1.233]Repeated measures analysis
Comparison: MMP-Degraded CRP, Week 2p-value: 0.63595% CI: [0.906, 1.173]Repeated measures analysis
Comparison: MMP-Degraded CRP, Week 4p-value: 0.86695% CI: [0.879, 1.165]Repeated measures analysis
Comparison: MMP-Degraded CRP, Week 6p-value: 0.7895% CI: [0.842, 1.139]Repeated measures analysis
Comparison: MMP-Degraded CRP, Week 8p-value: 0.21295% CI: [0.938, 1.32]Repeated measures analysis
Comparison: MMP-Degraded CRP, Week 12p-value: 0.24295% CI: [0.934, 1.3]Repeated measures analysis
Comparison: MMP-Degraded CRP, 12-Week FUp-value: 0.59795% CI: [0.87, 1.267]Repeated measures analysis
Comparison: MD1C, Week 1p-value: 0.04795% CI: [0.634, 0.997]Repeated measures analysis
Comparison: MD1C, Week 2p-value: 0.36795% CI: [0.668, 1.165]Repeated measures analysis
Comparison: MD1C, Week 4p-value: 0.15595% CI: [0.558, 1.102]Repeated measures analysis
Comparison: MD1C, Week 6p-value: 0.00495% CI: [0.477, 0.855]Repeated measures analysis
Comparison: MD1C, Week 8p-value: 0.1495% CI: [0.591, 1.08]Repeated measures analysis
Comparison: MD1C, Week 12p-value: 0.4795% CI: [0.647, 1.228]Repeated measures analysis
Comparison: MD1C, 12-Week FUp-value: 0.40195% CI: [0.621, 1.217]Repeated measures analysis
Comparison: MD2C, Week 1p-value: 0.88795% CI: [0.742, 1.296]Repeated measures analysis
Comparison: MD2C, Week 2p-value: 0.81495% CI: [0.744, 1.263]Repeated measures analysis
Comparison: MD2C, Week 4p-value: 0.79495% CI: [0.762, 1.233]Repeated measures analysis
Comparison: MD2C, Week 6p-value: 0.53995% CI: [0.696, 1.213]Repeated measures analysis
Comparison: MD2C, Week 8p-value: 0.62395% CI: [0.719, 1.221]Repeated measures analysis
Comparison: MD2C, Week 12p-value: 0.46795% CI: [0.711, 1.173]Repeated measures analysis
Comparison: MD2C, 12-Week FUp-value: 0.10895% CI: [0.57, 1.061]Repeated measures analysis
Comparison: MD3C, Week 1p-value: 0.89795% CI: [0.868, 1.175]Repeated measures analysis
Comparison: MD3C, Week 2p-value: 0.64495% CI: [0.884, 1.218]Repeated measures analysis
Comparison: MD3C, Week 4p-value: 0.5395% CI: [0.78, 1.139]Repeated measures analysis
Comparison: MD3C, Week 6p-value: 0.18295% CI: [0.733, 1.063]Repeated measures analysis
Comparison: MD3C, Week 8p-value: 0.69110% CI: [0.779, 1.182]Repeated measures analysis
Comparison: MD3C, Week 12p-value: 0.84395% CI: [0.79, 1.214]Repeated measures analysis
Comparison: MD3C, 12-Week FUp-value: 0.52495% CI: [0.855, 1.351]Repeated measures analysis
Primary
Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4)
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).
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 11.4 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C3, Week 8, n=7, 25 | 1.009 Ratio of complement biomarker | Geometric Coefficient of Variation 10.85 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C3, Week 12, n=7, 24 | 1.003 Ratio of complement biomarker | Geometric Coefficient of Variation 11.34 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C3, 12-Week FU, n=7, 22 | 0.995 Ratio of complement biomarker | Geometric Coefficient of Variation 10.65 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C4, Week 1, n=9, 25 | 0.969 Ratio of complement biomarker | Geometric Coefficient of Variation 13.13 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C4, Week 2, n=8, 26 | 0.984 Ratio of complement biomarker | Geometric Coefficient of Variation 16.45 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C4, Week 4, n=9, 27 | 0.945 Ratio of complement biomarker | Geometric Coefficient of Variation 14.63 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C4, Week 6, n=7, 27 | 0.985 Ratio of complement biomarker | Geometric Coefficient of Variation 17.32 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C4, Week 8, n=7, 25 | 1.006 Ratio of complement biomarker | Geometric Coefficient of Variation 13.53 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C4, Week 12, n=7, 24 | 0.994 Ratio of complement biomarker | Geometric Coefficient of Variation 12.75 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C4, 12-Week FU, n=7, 22 | 0.986 Ratio of complement biomarker | Geometric Coefficient of Variation 14.72 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C3, Week 1, n=9, 25 | 0.982 Ratio of complement biomarker | Geometric Coefficient of Variation 11.76 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C3, Week 2, n=8, 26 | 0.963 Ratio of complement biomarker | Geometric Coefficient of Variation 14.15 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C3, Week 4, n=9, 27 | 0.959 Ratio of complement biomarker | Geometric Coefficient of Variation 12.62 |
| GSK3196165 180 mg | Change From Baseline in Complement Biomarkers: Complement Component 3 (C3), Complement Component 4 (C4) | Complement C3, Week 6, n=7, 27 | 0.991 Ratio of complement biomarker | Geometric Coefficient of Variation 11.71 |
Primary
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)
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).
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 28.8 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 17.8 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | 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 | 0.994 Ratio of complement biomarker | Geometric Coefficient of Variation 28.84 |
| GSK3196165 180 mg | 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 | 0.990 Ratio of complement biomarker | Geometric Coefficient of Variation 67.63 |
| GSK3196165 180 mg | 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 | 1.156 Ratio of complement biomarker | Geometric Coefficient of Variation 75.77 |
| GSK3196165 180 mg | 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 | 1.100 Ratio of complement biomarker | Geometric Coefficient of Variation 46.87 |
| GSK3196165 180 mg | 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 | 0.860 Ratio of complement biomarker | Geometric Coefficient of Variation 53.87 |
| GSK3196165 180 mg | 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 | 0.998 Ratio of complement biomarker | Geometric Coefficient of Variation 60.41 |
| GSK3196165 180 mg | 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 | 0.901 Ratio of complement biomarker | Geometric Coefficient of Variation 93.48 |
| GSK3196165 180 mg | 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 | 1.221 Ratio of complement biomarker | Geometric Coefficient of Variation 56.53 |
| GSK3196165 180 mg | 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 | 0.991 Ratio of complement biomarker | Geometric Coefficient of Variation 29.67 |
| GSK3196165 180 mg | 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 | 1.015 Ratio of complement biomarker | Geometric Coefficient of Variation 55.6 |
| GSK3196165 180 mg | 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 | 1.010 Ratio of complement biomarker | Geometric Coefficient of Variation 35.63 |
| GSK3196165 180 mg | 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 | 1.044 Ratio of complement biomarker | Geometric Coefficient of Variation 33.94 |
| GSK3196165 180 mg | 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 | 0.957 Ratio of complement biomarker | Geometric Coefficient of Variation 26.95 |
| GSK3196165 180 mg | 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 | 0.995 Ratio of complement biomarker | Geometric Coefficient of Variation 29.49 |
| GSK3196165 180 mg | 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 | 1.130 Ratio of complement biomarker | Geometric Coefficient of Variation 32.16 |
| GSK3196165 180 mg | 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 | 1.020 Ratio of complement biomarker | Geometric Coefficient of Variation 43.7 |
| GSK3196165 180 mg | 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 | 1.040 Ratio of complement biomarker | Geometric Coefficient of Variation 60.64 |
| GSK3196165 180 mg | 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 | 1.126 Ratio of complement biomarker | Geometric Coefficient of Variation 41.04 |
| GSK3196165 180 mg | 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 | 1.084 Ratio of complement biomarker | Geometric Coefficient of Variation 53.9 |
| GSK3196165 180 mg | 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 | 1.055 Ratio of complement biomarker | Geometric Coefficient of Variation 67.53 |
| GSK3196165 180 mg | 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 | 0.843 Ratio of complement biomarker | Geometric Coefficient of Variation 72.14 |
| GSK3196165 180 mg | 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 | 1.041 Ratio of complement biomarker | Geometric Coefficient of Variation 38.6 |
| GSK3196165 180 mg | 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 | 0.963 Ratio of complement biomarker | Geometric Coefficient of Variation 16.38 |
| GSK3196165 180 mg | 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 | 0.954 Ratio of complement biomarker | Geometric Coefficient of Variation 17.14 |
| GSK3196165 180 mg | 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 | 0.947 Ratio of complement biomarker | Geometric Coefficient of Variation 27.1 |
| GSK3196165 180 mg | 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 | 0.959 Ratio of complement biomarker | Geometric Coefficient of Variation 30.14 |
| GSK3196165 180 mg | 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 | 0.950 Ratio of complement biomarker | Geometric Coefficient of Variation 28.73 |
| GSK3196165 180 mg | 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 | 0.915 Ratio of complement biomarker | Geometric Coefficient of Variation 35.29 |
Primary
Change From Baseline in Flow Cytometry: 6 Colour TB Natural Killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
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).
Time frame: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 15.1 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 12.8 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | 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 | 1.000 Ratio of biomarker | Geometric Coefficient of Variation 5.37 |
| GSK3196165 180 mg | 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 | 1.025 Ratio of biomarker | Geometric Coefficient of Variation 6.3 |
| GSK3196165 180 mg | 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 | 0.938 Ratio of biomarker | Geometric Coefficient of Variation 9.75 |
| GSK3196165 180 mg | 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 | 0.994 Ratio of biomarker | Geometric Coefficient of Variation 4.95 |
| GSK3196165 180 mg | 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 | 0.951 Ratio of biomarker | Geometric Coefficient of Variation 7.25 |
| GSK3196165 180 mg | 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 | 0.911 Ratio of biomarker | Geometric Coefficient of Variation 7.81 |
| GSK3196165 180 mg | 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 | 0.920 Ratio of biomarker | Geometric Coefficient of Variation 7.98 |
| GSK3196165 180 mg | 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 | 0.984 Ratio of biomarker | Geometric Coefficient of Variation 6.23 |
| GSK3196165 180 mg | 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 | 0.971 Ratio of biomarker | Geometric Coefficient of Variation 8.6 |
| GSK3196165 180 mg | 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 | 1.003 Ratio of biomarker | Geometric Coefficient of Variation 6.51 |
| GSK3196165 180 mg | 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 | 0.934 Ratio of biomarker | Geometric Coefficient of Variation 6.66 |
| GSK3196165 180 mg | 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 | 0.992 Ratio of biomarker | Geometric Coefficient of Variation 4.6 |
| GSK3196165 180 mg | 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 | 0.989 Ratio of biomarker | Geometric Coefficient of Variation 4.98 |
| GSK3196165 180 mg | 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 | 0.991 Ratio of biomarker | Geometric Coefficient of Variation 5.42 |
| GSK3196165 180 mg | 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 | 0.933 Ratio of biomarker | Geometric Coefficient of Variation 7.23 |
| GSK3196165 180 mg | 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 | 1.013 Ratio of biomarker | Geometric Coefficient of Variation 4.94 |
Comparison: CD16+CD56+, Week 1p-value: 0.78695% CI: [0.794, 1.354]Repeated measures analysis
Comparison: CD16+CD56+, Week 4p-value: 0.18895% CI: [0.603, 1.109]Repeated measures analysis
Comparison: CD16+CD56+, Week 12p-value: 0.12995% CI: [0.536, 1.087]Repeated measures analysis
Comparison: CD16+CD56+, 12-Week FUp-value: 0.05495% CI: [0.499, 1.006]Repeated measures analysis
Comparison: CD19, Week 1p-value: 0.38395% CI: [0.863, 1.45]Repeated measures analysis
Comparison: CD19, Week 4p-value: 0.5195% CI: [0.623, 1.271]Repeated measures analysis
Comparison: CD19, Week 12p-value: 0.72495% CI: [0.718, 1.262]Repeated measures analysis
Comparison: CD19, 12-Week FUp-value: 0.83195% CI: [0.635, 1.443]Repeated measures analysis
Comparison: CD3, Week 1p-value: 0.43795% CI: [0.882, 1.328]Repeated measures analysis
Comparison: CD3, Week 4p-value: 0.63295% CI: [0.711, 1.234]Repeated measures analysis
Comparison: CD3, Week 12p-value: 0.41395% CI: [0.885, 1.336]Repeated measures analysis
Comparison: CD3, 12-Week FUp-value: 0.56795% CI: [0.858, 1.316]Repeated measures analysis
Comparison: CD3+CD4+, Week 1p-value: 0.54795% CI: [0.855, 1.338]Repeated measures analysis
Comparison: CD3+CD4+, Week 4p-value: 0.51295% CI: [0.673, 1.223]Repeated measures analysis
Comparison: CD3+CD4+, Week 12p-value: 0.57395% CI: [0.853, 1.328]Repeated measures analysis
Comparison: CD3+CD4+, 12-Week FUp-value: 0.78995% CI: [0.818, 1.3]Repeated measures analysis
Primary
Change From Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL)
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).
Time frame: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 0.039 |
| Placebo | 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 0.058 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | 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 | -0.050 10^9 cells/Liter | Standard Error 0.1183 |
| GSK3196165 180 mg | 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 | -0.005 10^9 cells/Liter | Standard Error 0.0222 |
| GSK3196165 180 mg | 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 | -0.020 10^9 cells/Liter | Standard Error 0.0881 |
| GSK3196165 180 mg | 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 | -0.023 10^9 cells/Liter | Standard Error 0.0327 |
| GSK3196165 180 mg | 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 | -0.006 10^9 cells/Liter | Standard Error 0.0925 |
| GSK3196165 180 mg | 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 | -0.037 10^9 cells/Liter | Standard Error 0.0215 |
| GSK3196165 180 mg | 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 | -0.050 10^9 cells/Liter | Standard Error 0.1229 |
| GSK3196165 180 mg | 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 | -0.027 10^9 cells/Liter | Standard Error 0.0279 |
Comparison: CD3+CD8+, Week 1p-value: 0.42895% CI: [-0.056, 0.128]Repeated measures analysis
Comparison: CD3+CD8+, Week 4p-value: 0.73395% CI: [-0.159, 0.113]Repeated measures analysis
Comparison: CD3+CD8+, Week 12p-value: 0.67795% CI: [-0.076, 0.115]Repeated measures analysis
Comparison: CD3+CD8+, 12-Week FUp-value: 0.56995% CI: [-0.084, 0.151]Repeated measures analysis
Comparison: T Cell B Cell NKL, Week 1p-value: 0.56995% CI: [-0.263, 0.469]Repeated measures analysis
Comparison: T Cell B Cell NKL, Week 4p-value: 0.53495% CI: [-0.668, 0.354]Repeated measures analysis
Comparison: T Cell B Cell NKL, Week 12p-value: 0.66895% CI: [-0.323, 0.498]Repeated measures analysis
Comparison: T Cell B Cell NKL, 12-Week FUp-value: 0.93495% CI: [-0.526, 0.484]Repeated measures analysis
Primary
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+
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).
Time frame: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+ | 12-Week FU, n=5, 18 | -199.3 10^6 cells/Liter | Standard Error 219.73 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+ | Week 1, n=5, 19 | -380.9 10^6 cells/Liter | Standard Error 137.31 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+ | Week 12, n=5, 21 | -378.6 10^6 cells/Liter | Standard Error 229.47 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+ | Week 4, n=6, 22 | -41.5 10^6 cells/Liter | Standard Error 196.72 |
Comparison: Week 1p-value: 0.56495% CI: [-448.3, 804.6]Repeated measures analysis
Comparison: Week 4p-value: 0.21695% CI: [-335.7, 1416.5]Repeated measures analysis
Comparison: Week 12p-value: 0.62995% CI: [-1326, 820.8]Repeated measures analysis
Comparison: 12-Week FUp-value: 0.93295% CI: [-962.2, 1045.5]Repeated measures analysis
Primary
Change From Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
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).
Time frame: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 37788.7 |
| Placebo | 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 45766.7 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | 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 | 3992.8 10^3 cells/Liter | Standard Error 4134.52 |
| GSK3196165 180 mg | 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 | 738.7 10^3 cells/Liter | Standard Error 1266.25 |
| GSK3196165 180 mg | 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 | 17662.7 10^3 cells/Liter | Standard Error 21211.91 |
| GSK3196165 180 mg | 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 | 2278.8 10^3 cells/Liter | Standard Error 1696.12 |
| GSK3196165 180 mg | 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 | 4334.6 10^3 cells/Liter | Standard Error 3466.71 |
| GSK3196165 180 mg | 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 | 5453.0 10^3 cells/Liter | Standard Error 2399.11 |
| GSK3196165 180 mg | 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 | 10485.9 10^3 cells/Liter | Standard Error 12635.98 |
| GSK3196165 180 mg | 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 | 5474.0 10^3 cells/Liter | Standard Error 2439.59 |
| GSK3196165 180 mg | 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 | 759.2 10^3 cells/Liter | Standard Error 2534.27 |
| GSK3196165 180 mg | 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 | 1491.0 10^3 cells/Liter | Standard Error 2452.69 |
| GSK3196165 180 mg | 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 | 13201.2 10^3 cells/Liter | Standard Error 18684.22 |
| GSK3196165 180 mg | 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 | 2724.3 10^3 cells/Liter | Standard Error 3117.17 |
| GSK3196165 180 mg | 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 | 291.3 10^3 cells/Liter | Standard Error 1959.54 |
| GSK3196165 180 mg | 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 | 2668.0 10^3 cells/Liter | Standard Error 4589.28 |
| GSK3196165 180 mg | 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 | -31512.8 10^3 cells/Liter | Standard Error 24027.16 |
| GSK3196165 180 mg | 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 | 4800.0 10^3 cells/Liter | Standard Error 5266.23 |
Comparison: CD14-HLA-DR+CD11cbr+CD123-, Week 1p-value: 0.32895% CI: [-2953.7, 8466.3]Repeated measures analysis
Comparison: CD14-HLA-DR+CD11cbr+CD123-, Week 4p-value: 0.89595% CI: [-8003.7, 7028.6]Repeated measures analysis
Comparison: CD14-HLA-DR+CD11cbr+CD123-, Week 12p-value: 0.96195% CI: [-12001, 11446.2]Repeated measures analysis
Comparison: CD14-HLA-DR+CD11cbr+CD123-, 12-Week FUp-value: 0.95695% CI: [-11960.5, 11337.4]Repeated measures analysis
Comparison: CD14br+CD16+, Week 1p-value: 0.21295% CI: [-4230.7, 17964.6]Repeated measures analysis
Comparison: CD14br+CD16+, Week 4p-value: 0.22795% CI: [-5533.3, 22252.5]Repeated measures analysis
Comparison: CD14br+CD16+, Week 12p-value: 0.0495% CI: [-44298.5, -1068.8]Repeated measures analysis
Comparison: CD14br+CD16+, 12-Week FUp-value: 0.74195% CI: [-27146, 19631.6]Repeated measures analysis
Comparison: CD14br+CD16-, Week 1p-value: 0.62895% CI: [-116677.8, 71843.8]Repeated measures analysis
Comparison: CD14br+CD16-, Week 4p-value: 0.32195% CI: [-28567.8, 83887.1]Repeated measures analysis
Comparison: CD14br+CD16-, Week 12p-value: 0.70495% CI: [-70377, 102742.9]Repeated measures analysis
Comparison: CD14br+CD16-, 12-Week FUp-value: 0.23295% CI: [-170364.9, 43526.1]Repeated measures analysis
Comparison: CD14lo+CD16br+, Week 1p-value: 0.36695% CI: [-22588.4, 8761.1]Repeated measures analysis
Comparison: CD14lo+CD16br+, Week 4p-value: 0.60395% CI: [-10976.8, 6513.6]Repeated measures analysis
Comparison: CD14lo+CD16br+, Week 12p-value: 0.08495% CI: [-21827.4, 1469.2]Repeated measures analysis
Comparison: CD14lo+CD16br+, 12-Week FUp-value: 0.02695% CI: [-38771.8, -2716.5]Repeated measures analysis
Primary
Change From Baseline in Flow Cytometry: Helper/Suppressor Cells
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).
Time frame: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: Helper/Suppressor Cells | Helper/Suppressor, 12-Week FU, n=6, 21 | 1.065 Ratio of Helper/Suppressor cells | Geometric Coefficient of Variation 4.88 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: Helper/Suppressor Cells | Helper/Suppressor, Week 1, n=8, 25 | 0.976 Ratio of Helper/Suppressor cells | Geometric Coefficient of Variation 4 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: Helper/Suppressor Cells | Helper/Suppressor, Week 12, n=6, 25 | 1.088 Ratio of Helper/Suppressor cells | Geometric Coefficient of Variation 3.49 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: Helper/Suppressor Cells | Helper/Suppressor, Week 4, n=8, 25 | 0.998 Ratio of Helper/Suppressor cells | Geometric Coefficient of Variation 4.11 |
Comparison: Helper/Suppressor, Week 1p-value: 0.55895% CI: [0.809, 1.123]Repeated measures analysis
Comparison: Helper/Suppressor, Week 4p-value: 0.51595% CI: [0.801, 1.12]Repeated measures analysis
Comparison: Helper/Suppressor, Week 12p-value: 0.56595% CI: [0.895, 1.222]Repeated measures analysis
Comparison: Helper/Suppressor, 12-Week FUp-value: 0.89795% CI: [0.822, 1.249]Repeated measures analysis
Primary
Change From Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127-
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).
Time frame: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | 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 | -4.6 10^6 cells/Liter | Standard Error 3.15 |
| GSK3196165 180 mg | 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 | 2.9 10^6 cells/Liter | Standard Error 4.67 |
| GSK3196165 180 mg | 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 | -0.4 10^6 cells/Liter | Standard Error 4.7 |
| GSK3196165 180 mg | 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 | -3.1 10^6 cells/Liter | Standard Error 4.94 |
| GSK3196165 180 mg | 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 | 2.8 10^6 cells/Liter | Standard Error 3.58 |
| GSK3196165 180 mg | 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 | 2.0 10^6 cells/Liter | Standard Error 3.98 |
| GSK3196165 180 mg | 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 | -4.4 10^6 cells/Liter | Standard Error 3.91 |
| GSK3196165 180 mg | 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 | -2.3 10^6 cells/Liter | Standard Error 5.43 |
Comparison: CD3+CD4+CD25+CD127-, Week 1p-value: 0.50195% CI: [-13.1, 26.1]Repeated measures analysis
Comparison: CD3+CD4+CD25+CD127-, Week 4p-value: 0.85295% CI: [-21.6, 18]Repeated measures analysis
Comparison: CD3+CD4+CD25+CD127-, Week 12p-value: 0.57295% CI: [-16.4, 29]Repeated measures analysis
Comparison: CD3+CD4+CD25+CD127-, 12-Week FUp-value: 0.36395% CI: [-13, 34.1]Repeated measures analysis
Comparison: CD3+CD4+foxP3+CD25+CD127-, Week 1p-value: 0.78895% CI: [-13, 17]Repeated measures analysis
Comparison: CD3+CD4+foxP3+CD25+CD127-, Week 4p-value: 0.78695% CI: [-18.8, 14.4]Repeated measures analysis
Comparison: CD3+CD4+foxP3+CD25+CD127-, Week 12p-value: 0.43395% CI: [-25.4, 11.2]Repeated measures analysis
Comparison: CD3+CD4+foxP3+CD25+CD127-, 12-Week FUp-value: 0.5595% CI: [-9.8, 18]Repeated measures analysis
Primary
Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
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).
Time frame: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 10.5 |
| Placebo | 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 |
| Placebo | 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 11.7 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+ | CD3+, 12-Week FU, n=5, 17 | 0.991 Ratio of T Reg cell | Geometric Coefficient of Variation 6 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+ | CD3+ CD4+, Week 1, n=7, 23 | 1.007 Ratio of T Reg cell | Geometric Coefficient of Variation 5.65 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+ | CD3+ CD4+, Week 4, n=7, 22 | 0.976 Ratio of T Reg cell | Geometric Coefficient of Variation 6.38 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+ | CD3+ CD4+, Week 12, n=5, 21 | 1.004 Ratio of T Reg cell | Geometric Coefficient of Variation 5.31 |
| GSK3196165 180 mg | 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 | 1.003 Ratio of T Reg cell | Geometric Coefficient of Variation 6.39 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+ | CD3+ CD8+, Week 1, n=7, 23 | 0.983 Ratio of T Reg cell | Geometric Coefficient of Variation 5.5 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+ | CD3+ CD8+, Week 4, n=7, 22 | 0.939 Ratio of T Reg cell | Geometric Coefficient of Variation 6.66 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+ | CD3+ CD8+, Week 12, n=5, 21 | 0.945 Ratio of T Reg cell | Geometric Coefficient of Variation 5.4 |
| GSK3196165 180 mg | 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 | 0.965 Ratio of T Reg cell | Geometric Coefficient of Variation 6.05 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+ | CD3+, Week 1, n=7, 23 | 0.992 Ratio of T Reg cell | Geometric Coefficient of Variation 5.54 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+ | CD3+, Week 4, n=7, 22 | 0.938 Ratio of T Reg cell | Geometric Coefficient of Variation 7.33 |
| GSK3196165 180 mg | Change From Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+ | CD3+, Week 12, n=5, 21 | 0.993 Ratio of T Reg cell | Geometric Coefficient of Variation 4.9 |
Comparison: CD3+ CD4+, Week 1p-value: 0.36995% CI: [0.876, 1.412]Repeated measures analysis
Comparison: CD3+ CD4+, Week 4p-value: 0.64195% CI: [0.721, 1.228]Repeated measures analysis
Comparison: CD3+ CD4+, Week 12p-value: 0.84495% CI: [0.804, 1.303]Repeated measures analysis
Comparison: CD3+ CD4+, 12-Week FUp-value: 0.55895% CI: [0.821, 1.427]Repeated measures analysis
Comparison: CD3+ CD8+, Week 1p-value: 0.36395% CI: [0.88, 1.402]Repeated measures analysis
Comparison: CD3+ CD8+, Week 4p-value: 0.75195% CI: [0.724, 1.265]Repeated measures analysis
Comparison: CD3+ CD8+, Week 12p-value: 0.53795% CI: [0.846, 1.37]Repeated measures analysis
Comparison: CD3+ CD8+, 12-Week FUp-value: 0.80695% CI: [0.797, 1.335]Repeated measures analysis
Comparison: CD3+, Week 1p-value: 0.40595% CI: [0.872, 1.391]Repeated measures analysis
Comparison: CD3+, Week 4p-value: 0.51995% CI: [0.668, 1.232]Repeated measures analysis
Comparison: CD3+, Week 12p-value: 0.74895% CI: [0.831, 1.291]Repeated measures analysis
Comparison: CD3+, 12-Week FUp-value: 0.70495% CI: [0.811, 1.356]Repeated measures analysis
Primary
Change From Baseline in Mechanistic Biomarkers
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).
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 4, n=9, 27 | 1.000 Ratio of mechanistic biomarker | — |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Interleukin 15, Week 1, n=9, 27 | 1.001 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 12.7 |
| Placebo | 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 |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 8, n=7, 25 | 1.000 Ratio of mechanistic biomarker | — |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Interleukin 17F, Week 8, n=7, 25 | 0.947 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 19.2 |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 2, n=8, 26 | 1.000 Ratio of mechanistic biomarker | — |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 12, n=7, 24 | 1.000 Ratio of mechanistic biomarker | — |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Interleukin 8, Week 4, n=9, 27 | 1.102 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 38.3 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 6, n=7, 27 | 1.000 Ratio of mechanistic biomarker | — |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Tumor Necrosis Factor, Week 1, n=9, 26 | 0.976 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 15.2 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Tumor Necrosis Factor, Week 4, n=9, 27 | 0.933 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 17.7 |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, 12-Week FU, n=7, 21 | 1.000 Ratio of mechanistic biomarker | — |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Interleukin 17 Alpha, Week 6, n=7, 26 | 1.015 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 76.6 |
| Placebo | 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 |
| Placebo | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 1, n=9, 26 | 1.000 Ratio of mechanistic biomarker | — |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Tumor Necrosis Factor,12-Week FU, n=7, 21 | 1.057 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 34.72 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 1, n=9, 26 | 1.000 Ratio of mechanistic biomarker | — |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 2, n=8, 26 | 1.000 Ratio of mechanistic biomarker | — |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 4, n=9, 27 | 1.000 Ratio of mechanistic biomarker | — |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 6, n=7, 27 | 1.000 Ratio of mechanistic biomarker | — |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 8, n=7, 25 | 1.000 Ratio of mechanistic biomarker | — |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, Week 12, n=7, 24 | 1.000 Ratio of mechanistic biomarker | — |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 1 Beta, 12-Week FU, n=7, 21 | 1.000 Ratio of mechanistic biomarker | — |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 10, Week 1, n=9, 26 | 0.994 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 28.47 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 10, Week 2, n=8, 26 | 1.048 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 37.27 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 10, Week 4, n=9, 27 | 0.985 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 32.52 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 10, Week 6, n=7, 27 | 0.960 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 17.66 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 10, Week 8, n=7, 25 | 0.969 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 30.23 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 10, Week 12, n=7, 24 | 0.989 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 21.36 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 10, 12-Week FU, n=7, 21 | 1.230 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 62.91 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 15, Week 1, n=9, 27 | 0.950 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 59.23 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 15, Week 2, n=8, 26 | 0.849 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 102.76 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 15, Week 4, n=9, 27 | 0.831 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 84.07 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 15, Week 6, n=7, 27 | 0.904 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 90.53 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 15, Week 8, n=7, 25 | 0.865 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 90.3 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 15, Week 12, n=7, 24 | 0.771 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 82.21 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 15, 12-Week FU, n=7, 21 | 0.636 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 111.86 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17 Alpha, Week 1, n=9, 25 | 1.054 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 93.04 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17 Alpha, Week 2, n=8, 25 | 0.942 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 72.24 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17 Alpha, Week 4, n=9, 26 | 0.911 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 102.66 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17 Alpha, Week 6, n=7, 26 | 0.867 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 90.15 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17 Alpha, Week 8, n=7, 23 | 1.005 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 135.76 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17 Alpha, Week 12, n=7, 23 | 0.857 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 101.45 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17 Alpha, 12-Week FU, n=7, 20 | 0.999 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 150.12 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17F, Week 1, n=9, 25 | 0.797 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 78.96 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17F, Week 2, n=8, 26 | 0.911 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 72.36 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17F, Week 4, n=9, 26 | 0.948 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 89.47 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17F, Week 6, n=7, 25 | 1.013 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 107.49 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17F, Week 8, n=7, 25 | 0.815 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 91.93 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17F, Week 12, n=7, 23 | 0.884 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 100.03 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 17F, 12-Week FU, n=7, 21 | 0.741 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 90.62 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 8, Week 1, n=9, 26 | 1.081 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 74.78 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 8, Week 2, n=8, 26 | 0.861 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 78.64 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 8, Week 4, n=9, 27 | 0.773 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 82.48 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 8, Week 6, n=7, 27 | 0.720 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 72.7 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 8, Week 8, n=7, 25 | 0.761 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 80.51 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 8, Week 12, n=7, 24 | 0.850 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 80.98 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Interleukin 8, 12-Week FU, n=7, 21 | 0.841 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 96.92 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Tumor Necrosis Factor, Week 1, n=9, 26 | 0.994 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 18.45 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Tumor Necrosis Factor, Week 2, n=8, 26 | 0.977 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 16.81 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Tumor Necrosis Factor, Week 4, n=9, 27 | 0.871 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 48.19 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Tumor Necrosis Factor, Week 6, n=7, 27 | 0.929 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 21.48 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Tumor Necrosis Factor, Week 8, n=7, 25 | 0.930 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 20.85 |
| GSK3196165 180 mg | Change From Baseline in Mechanistic Biomarkers | Tumor Necrosis Factor, Week 12, n=7, 24 | 0.969 Ratio of mechanistic biomarker | Geometric Coefficient of Variation 29.74 |
Primary
Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
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).
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 20.9 |
| Placebo | 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 |
| Placebo | 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 15.2 |
| Placebo | 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 |
| Placebo | 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 19.2 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 20.6 |
| GSK3196165 180 mg | 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 | 0.812 Ratio of predictive biomarker | Geometric Coefficient of Variation 11.81 |
| GSK3196165 180 mg | 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 | 0.986 Ratio of predictive biomarker | Geometric Coefficient of Variation 2.16 |
| GSK3196165 180 mg | 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 | 0.939 Ratio of predictive biomarker | Geometric Coefficient of Variation 8.92 |
| GSK3196165 180 mg | 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 | 0.986 Ratio of predictive biomarker | Geometric Coefficient of Variation 6.7 |
| GSK3196165 180 mg | 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 | 0.879 Ratio of predictive biomarker | Geometric Coefficient of Variation 12.05 |
| GSK3196165 180 mg | 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 | 0.838 Ratio of predictive biomarker | Geometric Coefficient of Variation 9.55 |
| GSK3196165 180 mg | 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 | 0.823 Ratio of predictive biomarker | Geometric Coefficient of Variation 8.65 |
| GSK3196165 180 mg | 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 | 0.833 Ratio of predictive biomarker | Geometric Coefficient of Variation 8.88 |
| GSK3196165 180 mg | 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 | 0.857 Ratio of predictive biomarker | Geometric Coefficient of Variation 11.46 |
| GSK3196165 180 mg | 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 | 0.842 Ratio of predictive biomarker | Geometric Coefficient of Variation 8.48 |
| GSK3196165 180 mg | 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 | 0.889 Ratio of predictive biomarker | Geometric Coefficient of Variation 11.26 |
| GSK3196165 180 mg | 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 | 0.897 Ratio of predictive biomarker | Geometric Coefficient of Variation 11.89 |
| GSK3196165 180 mg | 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 | 1.018 Ratio of predictive biomarker | Geometric Coefficient of Variation 11.83 |
| GSK3196165 180 mg | 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 | 0.893 Ratio of predictive biomarker | Geometric Coefficient of Variation 13.45 |
Comparison: 14-3-3 ETA Protein, Week 1p-value: 0.19395% CI: [0.861, 1.032]Repeated measures analysis
Comparison: 14-3-3 ETA Protein, Week 2p-value: 0.84295% CI: [0.776, 1.362]Repeated measures analysis
Comparison: 14-3-3 ETA Protein, Week 4p-value: 0.12795% CI: [0.505, 1.093]Repeated measures analysis
Comparison: 14-3-3 ETA Protein, Week 6p-value: 0.13795% CI: [0.531, 1.095]Repeated measures analysis
Comparison: 14-3-3 ETA Protein, Week 8p-value: 0.48895% CI: [0.623, 1.259]Repeated measures analysis
Comparison: 14-3-3 ETA Protein, Week 12p-value: 0.33895% CI: [0.488, 1.29]Repeated measures analysis
Comparison: 14-3-3 ETA Protein, 12-Week FUp-value: 0.58295% CI: [0.491, 1.502]Repeated measures analysis
Comparison: S100 CBP A8 and A9, Week 1p-value: 0.99695% CI: [0.699, 1.427]Repeated measures analysis
Comparison: S100 CBP A8 and A9, Week 2p-value: 0.74595% CI: [0.662, 1.346]Repeated measures analysis
Comparison: S100 CBP A8 and A9, Week 4p-value: 0.93995% CI: [0.649, 1.593]Repeated measures analysis
Comparison: S100 CBP A8 and A9, Week 6p-value: 0.93795% CI: [0.595, 1.617]Repeated measures analysis
Comparison: S100 CBP A8 and A9, Week 8p-value: 0.78795% CI: [0.659, 1.727]Repeated measures analysis
Comparison: S100 CBP A8 and A9, Week 12p-value: 0.34295% CI: [0.769, 2.086]Repeated measures analysis
Comparison: S100 CBP A8 and A9, 12-Week FUp-value: 0.02695% CI: [1.076, 2.838]Repeated measures analysis
Primary
Change From Baseline in Predictive Biomarkers: Amyloid A
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.
Time frame: Baseline and Week 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Amyloid A | Amyloid A, Week 12, n=7, 24 | 0.653 Ratio of predictive biomarker | Geometric Coefficient of Variation 25.45 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Amyloid A | Amyloid A, 12-Week FU, n=7, 21 | 0.623 Ratio of predictive biomarker | Geometric Coefficient of Variation 19.68 |
Comparison: Amyloid A, Week 12p-value: 0.63295% CI: [0.261, 2.29]Repeated measures analysis
Comparison: Amyloid A, 12-Week FUp-value: 0.68595% CI: [0.519, 2.663]Repeated measures analysis
Primary
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
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.
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 17.2 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 23.7 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | 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 | 1.321 Ratio of predictive biomarker | Geometric Coefficient of Variation 7.53 |
| GSK3196165 180 mg | 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 | 0.773 Ratio of predictive biomarker | Geometric Coefficient of Variation 10.94 |
| GSK3196165 180 mg | 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 | 0.651 Ratio of predictive biomarker | Geometric Coefficient of Variation 13.6 |
| GSK3196165 180 mg | 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 | 0.679 Ratio of predictive biomarker | Geometric Coefficient of Variation 12.51 |
| GSK3196165 180 mg | 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 | 0.779 Ratio of predictive biomarker | Geometric Coefficient of Variation 12.48 |
| GSK3196165 180 mg | 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 | 0.675 Ratio of predictive biomarker | Geometric Coefficient of Variation 11.21 |
| GSK3196165 180 mg | 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 | 0.890 Ratio of predictive biomarker | Geometric Coefficient of Variation 13.9 |
| GSK3196165 180 mg | 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 | 1.357 Ratio of predictive biomarker | Geometric Coefficient of Variation 13.59 |
| GSK3196165 180 mg | 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 | 0.915 Ratio of predictive biomarker | Geometric Coefficient of Variation 8.87 |
| GSK3196165 180 mg | 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 | 1.095 Ratio of predictive biomarker | Geometric Coefficient of Variation 7.78 |
| GSK3196165 180 mg | 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 | 1.170 Ratio of predictive biomarker | Geometric Coefficient of Variation 8.9 |
| GSK3196165 180 mg | 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 | 1.038 Ratio of predictive biomarker | Geometric Coefficient of Variation 8.91 |
| GSK3196165 180 mg | 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 | 1.021 Ratio of predictive biomarker | Geometric Coefficient of Variation 12.38 |
| GSK3196165 180 mg | 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 | 1.077 Ratio of predictive biomarker | Geometric Coefficient of Variation 16.31 |
| GSK3196165 180 mg | 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 | 1.224 Ratio of predictive biomarker | Geometric Coefficient of Variation 15.04 |
| GSK3196165 180 mg | 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 | 1.064 Ratio of predictive biomarker | Geometric Coefficient of Variation 16.38 |
| GSK3196165 180 mg | 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 | 0.830 Ratio of predictive biomarker | Geometric Coefficient of Variation 16.63 |
| GSK3196165 180 mg | 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 | 0.811 Ratio of predictive biomarker | Geometric Coefficient of Variation 15.1 |
| GSK3196165 180 mg | 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 | 0.748 Ratio of predictive biomarker | Geometric Coefficient of Variation 13.51 |
| GSK3196165 180 mg | 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 | 0.872 Ratio of predictive biomarker | Geometric Coefficient of Variation 13.35 |
| GSK3196165 180 mg | 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 | 0.939 Ratio of predictive biomarker | Geometric Coefficient of Variation 12.35 |
| GSK3196165 180 mg | 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 | 1.308 Ratio of predictive biomarker | Geometric Coefficient of Variation 18.63 |
| GSK3196165 180 mg | 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 | 0.914 Ratio of predictive biomarker | Geometric Coefficient of Variation 2.89 |
| GSK3196165 180 mg | 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 | 0.911 Ratio of predictive biomarker | Geometric Coefficient of Variation 4.15 |
| GSK3196165 180 mg | 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 | 0.895 Ratio of predictive biomarker | Geometric Coefficient of Variation 4.67 |
| GSK3196165 180 mg | 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 | 0.994 Ratio of predictive biomarker | Geometric Coefficient of Variation 4.48 |
| GSK3196165 180 mg | 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 | 0.899 Ratio of predictive biomarker | Geometric Coefficient of Variation 5.09 |
| GSK3196165 180 mg | 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 | 1.058 Ratio of predictive biomarker | Geometric Coefficient of Variation 5.23 |
Comparison: CL17, Week 1p-value: 0.09795% CI: [0.445, 1.074]Repeated measures analysis
Comparison: CL17, Week 2p-value: 0.22995% CI: [0.407, 1.249]Repeated measures analysis
Comparison: CL17, Week 4p-value: 0.05595% CI: [0.365, 1.012]Repeated measures analysis
Comparison: CL17, Week 6p-value: 0.30795% CI: [0.435, 1.309]Repeated measures analysis
Comparison: CL17, Week 8p-value: 0.01795% CI: [0.348, 0.894]Repeated measures analysis
p-value: 0.02695% CI: [0.294, 0.922]Repeated measures analysis
Comparison: CL17, 12-Week FUp-value: 0.83995% CI: [0.548, 1.636]Repeated measures analysis
Comparison: CL13, Week 1p-value: 0.14295% CI: [0.53, 1.1]Repeated measures analysis
Comparison: CL13, Week 2p-value: 0.97695% CI: [0.726, 1.39]Repeated measures analysis
Comparison: CL13, Week 4p-value: 0.24495% CI: [0.859, 1.778]Repeated measures analysis
Comparison: CL13, Week 6p-value: 0.27895% CI: [0.836, 1.83]Repeated measures analysis
Comparison: CL13, Week 8p-value: 0.67795% CI: [0.651, 1.92]Repeated measures analysis
Comparison: CL13, Week 12p-value: 0.66195% CI: [0.573, 2.369]Repeated measures analysis
Comparison: CL13, 12-Week FUp-value: 0.15495% CI: [0.832, 3.007]Repeated measures analysis
Comparison: Interleukin 6, Week 1p-value: 0.75195% CI: [0.471, 1.729]Repeated measures analysis
Comparison: Interleukin 6, Week 2p-value: 0.3395% CI: [0.367, 1.413]Repeated measures analysis
Comparison: Interleukin 6, Week 4p-value: 0.51995% CI: [0.447, 1.512]Repeated measures analysis
Comparison: Interleukin 6, Week 6p-value: 0.14795% CI: [0.372, 1.167]Repeated measures analysis
Comparison: Interleukin 6, Week 8p-value: 0.16695% CI: [0.396, 1.18]Repeated measures analysis
Comparison: Interleukin 6, Week 12p-value: 0.43295% CI: [0.734, 2.031]Repeated measures analysis
Comparison: Interleukin 6, 12-Week FUp-value: 0.21695% CI: [0.75, 3.423]Repeated measures analysis
Comparison: MDC, Week 1p-value: 0.19595% CI: [0.823, 1.042]Repeated measures analysis
Comparison: MDC, Week 2p-value: 0.85195% CI: [0.829, 1.168]Repeated measures analysis
Comparison: MDC, Week 4p-value: 0.63795% CI: [0.79, 1.158]Repeated measures analysis
Comparison: MDC, Week 6p-value: 0.91595% CI: [0.833, 1.225]Repeated measures analysis
Comparison: MDC, Week 8p-value: 0.15795% CI: [0.69, 1.064]Repeated measures analysis
Comparison: MDC, Week 12p-value: 0.14295% CI: [0.681, 1.059]Repeated measures analysis
Comparison: MDC, 12-Week FUp-value: 0.92995% CI: [0.745, 1.378]Repeated measures analysis
Primary
Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
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).
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 8.3 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | MMP-3, Week 6, n=7, 27 | 0.804 Ratio of predictive biomarker | Geometric Coefficient of Variation 13.44 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | Chitinase 3 Like 1, Week 1, n=9, 27 | 0.917 Ratio of predictive biomarker | Geometric Coefficient of Variation 8.13 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | MMP 3, Week 1, n=9, 27 | 0.984 Ratio of predictive biomarker | Geometric Coefficient of Variation 3.88 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | Chitinase 3 Like 1, Week 2, n=8, 26 | 0.966 Ratio of predictive biomarker | Geometric Coefficient of Variation 8.55 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | MMP-3, Week 12, n=7, 24 | 0.951 Ratio of predictive biomarker | Geometric Coefficient of Variation 7.35 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | Chitinase 3 Like 1, Week 4, n=9, 27 | 1.088 Ratio of predictive biomarker | Geometric Coefficient of Variation 9.96 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | MMP-3, Week 2, n=8, 26 | 1.024 Ratio of predictive biomarker | Geometric Coefficient of Variation 4.09 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | Chitinase 3 Like 1, Week 6, n=7, 27 | 1.031 Ratio of predictive biomarker | Geometric Coefficient of Variation 8.8 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | MMP-3, Week 8, n=7, 25 | 1.088 Ratio of predictive biomarker | Geometric Coefficient of Variation 8.21 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | Chitinase 3 Like 1, Week 8, n=7, 25 | 0.947 Ratio of predictive biomarker | Geometric Coefficient of Variation 9.7 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | MMP-3, Week 4, n=9, 27 | 1.016 Ratio of predictive biomarker | Geometric Coefficient of Variation 4.73 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | Chitinase 3 Like 1, Week 12, n=7, 24 | 1.071 Ratio of predictive biomarker | Geometric Coefficient of Variation 11.64 |
| GSK3196165 180 mg | Change From Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3) | MMP-3, 12-Week FU, n=7, 21 | 0.984 Ratio of predictive biomarker | Geometric Coefficient of Variation 9 |
| GSK3196165 180 mg | 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 | 1.019 Ratio of predictive biomarker | Geometric Coefficient of Variation 9.75 |
Comparison: MMP-3, Week 2p-value: 0.62195% CI: [0.809, 1.137]Repeated measures analysis
Comparison: Chitinase 3 Like 1, Week 1p-value: 0.46395% CI: [0.64, 1.231]Repeated measures analysis
Comparison: Chitinase 3 Like 1, Week 2p-value: 0.78295% CI: [0.672, 1.352]Repeated measures analysis
Comparison: Chitinase 3 Like 1, Week 4p-value: 0.53395% CI: [0.759, 1.69]Repeated measures analysis
Comparison: Chitinase 3 Like 1, Week 6p-value: 0.47395% CI: [0.779, 1.694]Repeated measures analysis
Comparison: Chitinase 3 Like 1, Week 8p-value: 0.60895% CI: [0.733, 1.687]Repeated measures analysis
Comparison: Chitinase 3 Like 1, Week 12p-value: 0.98595% CI: [0.613, 1.645]Repeated measures analysis
Comparison: Chitinase 3 Like 1, 12-Week FUp-value: 0.10295% CI: [0.934, 2.057]Repeated measures analysis
Comparison: MMP-3, Week 1p-value: 0.25995% CI: [0.781, 1.071]Repeated measures analysis
Comparison: MMP-3, Week 4p-value: 0.35495% CI: [0.752, 1.11]Repeated measures analysis
Comparison: MMP-3, Week 6p-value: 0.44895% CI: [0.443, 1.444]Repeated measures analysis
Comparison: MMP-3, Week 8p-value: 0.40295% CI: [0.813, 1.653]Repeated measures analysis
Comparison: MMP-3, Week 12p-value: 0.74595% CI: [0.695, 1.301]Repeated measures analysis
Comparison: MMP-3, 12-Week FUp-value: 0.27995% CI: [0.837, 1.796]Repeated measures analysis
Primary
Change From Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D
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).
Time frame: Baseline and Week 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 23.1 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D | Surfactant Protein D, 12-Week FU, n=7, 21 | 0.985 Ratio of safety biomarker | Geometric Coefficient of Variation 31.32 |
| GSK3196165 180 mg | Change From Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D | 3B-Cholestenoic Acid, Week 12, n=7, 24 | 1.094 Ratio of safety biomarker | Geometric Coefficient of Variation 19.45 |
| GSK3196165 180 mg | Change From Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D | Surfactant Protein D, Week 12, n=7, 24 | 1.134 Ratio of safety biomarker | Geometric Coefficient of Variation 27.96 |
| GSK3196165 180 mg | Change From Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D | 3B-Cholestenoic Acid, Week 22, n=7, 22 | 1.009 Ratio of safety biomarker | Geometric Coefficient of Variation 22.67 |
Primary
Change From Baseline in Safety Biomarkers: KL-6 Antigen
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).
Time frame: Baseline and Week 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in Safety Biomarkers: KL-6 Antigen | Week 12, n=6, 24 | 1.099 Ratio of safety biomarker | Geometric Coefficient of Variation 66.17 |
| GSK3196165 180 mg | Change From Baseline in Safety Biomarkers: KL-6 Antigen | 12-Week FU, n=6, 21 | 1.024 Ratio of safety biomarker | Geometric Coefficient of Variation 93.56 |
Primary
Change From Baseline in Target Engagement Biomarkers- Soluble Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) Complexed to GSK3196165
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).
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week follow-up (FU) (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 41.8 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 20.8 |
| Placebo | 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 |
| GSK3196165 180 mg | 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 | 1.176 Ratio of GM-CSF complex | Geometric Coefficient of Variation 12.88 |
| GSK3196165 180 mg | 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 | 13.799 Ratio of GM-CSF complex | Geometric Coefficient of Variation 20.65 |
| GSK3196165 180 mg | 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 | 31.056 Ratio of GM-CSF complex | Geometric Coefficient of Variation 17.58 |
| GSK3196165 180 mg | 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 | 53.496 Ratio of GM-CSF complex | Geometric Coefficient of Variation 18.55 |
| GSK3196165 180 mg | 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 | 46.620 Ratio of GM-CSF complex | Geometric Coefficient of Variation 22.37 |
| GSK3196165 180 mg | 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 | 33.404 Ratio of GM-CSF complex | Geometric Coefficient of Variation 22.47 |
| GSK3196165 180 mg | 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 | 22.556 Ratio of GM-CSF complex | Geometric Coefficient of Variation 24.38 |
Comparison: GM-CSF - Complex, Week 1p-value: <0.00195% CI: [6.251, 32.262]Repeated measures analysis
Comparison: GM-CSF - Complex, Week 2p-value: <0.00195% CI: [15.828, 66.156]Repeated measures analysis
Comparison: GM-CSF - Complex, Week 4p-value: <0.00195% CI: [25.646, 121.287]Repeated measures analysis
Comparison: GM-CSF - Complex, Week 6p-value: <0.00195% CI: [19.341, 120.798]Repeated measures analysis
Comparison: GM-CSF - Complex, Week 8p-value: <0.00195% CI: [13.69, 87.629]Repeated measures analysis
Comparison: GM-CSF - Complex, Week 12p-value: <0.00195% CI: [8.579, 63.005]Repeated measures analysis
Comparison: GM-CSF - Complex, 12-Week FUp-value: 0.40195% CI: [0.742, 2.048]Repeated measures analysis
Primary
Change From Baseline in T Helper Cell Panel Events
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).
Time frame: Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 13.5 |
| Placebo | 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 |
| Placebo | 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 37.8 |
| Placebo | 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 |
| Placebo | 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 6.8 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 25.9 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 33.5 |
| Placebo | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+, Week 1, n=7, 23 | -3845.3 Events | Standard Error 2648.6 |
| Placebo | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+, Week 4, n=7, 21 | 1622.8 Events | Standard Error 2973.6 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 393.1 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 2413.9 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+, Week 4, n=7, 21 | 1075.1 Events | Standard Error 1723.09 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6-CXCR3+, 12-Week FU, n=5, 18 | 607.0 Events | Standard Error 927.11 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 1, n=7, 23 | -34.0 Events | Standard Error 7.35 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | vCD45+CD3+CD8-CD4+, Week 12, n=5, 22 | 1006.9 Events | Standard Error 2026.47 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 4, n=7, 21 | -6.1 Events | Standard Error 10.63 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6-CXCR3-, 12-Week FU, n=5, 18 | -1316.7 Events | Standard Error 892.55 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 12, n=5, 22 | -6.9 Events | Standard Error 17.69 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+, 12-Week FU, n=5, 18 | -1832.0 Events | Standard Error 1366.65 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6+CXCR3+38+DR+,12-Week FU,n=5,18 | -18.7 Events | Standard Error 8.66 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 1, n=7, 23 | 1521.8 Events | Standard Error 547.18 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 1, n=7, 23 | -10.5 Events | Standard Error 3.62 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 1, n=7, 23 | -1030.2 Events | Standard Error 345.07 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 4, n=7, 21 | 12.2 Events | Standard Error 9.1 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 1, n=7, 23 | 45.4 Events | Standard Error 1187.37 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 12, n=5, 22 | -3.0 Events | Standard Error 7.55 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 4, n=7, 21 | -316.5 Events | Standard Error 438.76 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6+CXCR3-38+DR+, 12-Week FU, n=5, 18 | 3.3 Events | Standard Error 6.36 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 4, n=7, 21 | -292.5 Events | Standard Error 967 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 1, n=7, 23 | -129.2 Events | Standard Error 46.04 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 12, n=5, 22 | -506.4 Events | Standard Error 389.97 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 4, n=7, 21 | -108.0 Events | Standard Error 35.05 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 12, n=5, 22 | 161.4 Events | Standard Error 1209.82 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 12, n=5, 22 | 77.7 Events | Standard Error 146.73 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6+CXCR3+, 12-Week FU, n=5, 18 | -463.0 Events | Standard Error 412.22 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6-CXCR3+38+DR+, 12-Week FU, n=5, 18 | -104.0 Events | Standard Error 34.73 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 12, n=5, 22 | 1443.1 Events | Standard Error 1209.66 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 1, n=7, 23 | -70.5 Events | Standard Error 14.03 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 1, n=7, 23 | -654.5 Events | Standard Error 212.18 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 4, n=7, 21 | -56.3 Events | Standard Error 17.93 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 4, n=7, 21 | 1637.6 Events | Standard Error 1665.46 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 12, n=5, 22 | 43.0 Events | Standard Error 92.38 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 4, n=7, 21 | 14.2 Events | Standard Error 277.06 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+3+8-4+CCR6-CXCR3-38+DR+, 12-Week FU, n=5, 18 | -59.9 Events | Standard Error 17.32 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6+CXCR3-, 12-Week FU, n=5, 18 | -509.2 Events | Standard Error 291.09 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+, Week 1, n=7, 23 | -163.0 Events | Standard Error 1444.61 |
| GSK3196165 180 mg | Change From Baseline in T Helper Cell Panel Events | CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 12, n=5, 22 | -219.7 Events | Standard Error 253.92 |
Comparison: CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 1p-value: 0.3595% CI: [-16.9, 46.1]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 4p-value: 0.69795% CI: [-35.3, 52]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 12p-value: 0.24995% CI: [-135.2, 36.8]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6+CXCR3+38+DR+, 12-Week FUp-value: 0.11995% CI: [-68.6, 8.3]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 1p-value: 0.40395% CI: [-9.3, 22.4]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 4p-value: 0.9195% CI: [-39.4, 35.2]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 12p-value: 0.71895% CI: [-43.1, 30.1]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6+CXCR3-38+DR+, 12-Week FUp-value: 0.68795% CI: [-34.4, 23]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 1p-value: 0.55995% CI: [-249.8, 137.7]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 4p-value: 0.4795% CI: [-93.9, 197]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 12p-value: 0.67595% CI: [-829.2, 546.3]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6-CXCR3+38+DR+, 12-Week FUp-value: 0.0895% CI: [-294, 18.2]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 1p-value: 0.98995% CI: [-60.5, 61.3]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 4p-value: 0.63495% CI: [-94.3, 59.6]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 12p-value: 0.78995% CI: [-395.2, 513.9]Repeated measures analysis
Comparison: CD45+3+8-4+CCR6-CXCR3-38+DR+, 12-Week FUp-value: 0.24995% CI: [-135.5, 41]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+, Week 1p-value: 0.23495% CI: [-2511.9, 9876.5]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+, Week 4p-value: 0.87595% CI: [-7612.6, 6517.3]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+, Week 12p-value: 0.81595% CI: [-10706, 8494.1]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+, 12-Week FUp-value: 0.2395% CI: [-9738.9, 2476.8]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 1p-value: 0.48995% CI: [-2021.4, 990.1]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 4p-value: 0.82295% CI: [-2001.7, 1602]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 12p-value: 0.78495% CI: [-2136.7, 1629.7]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6+CXCR3+, 12-Week FUp-value: 0.80495% CI: [-1633.1, 2083.2]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 1p-value: 0.71995% CI: [-754.5, 1079.9]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 4p-value: 0.74295% CI: [-1317.4, 950.3]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 12p-value: 0.65895% CI: [-1507.5, 970.5]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6+CXCR3-, 12-Week FUp-value: 0.75595% CI: [-1499.3, 1104.2]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 1p-value: 0.33395% CI: [-1250, 3550]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 4p-value: 0.89195% CI: [-4269.2, 3733.3]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 12p-value: 0.63395% CI: [-7073.1, 4378.3]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6-CXCR3+, 12-Week FUp-value: 0.4195% CI: [-5864.1, 2486.2]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 1p-value: 0.19695% CI: [-1786, 8339.6]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 4p-value: 0.89495% CI: [-7285.5, 6390.8]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 12p-value: 0.695% CI: [-4101.4, 6972]Repeated measures analysis
Comparison: CD45+CD3+CD8-CD4+CCR6-CXCR3-, 12-Week FUp-value: 0.53495% CI: [-5213.1, 2792.7]Repeated measures analysis
Secondary
Change From Baseline in Erosion as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist
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.
Time frame: Baseline and Weeks 4, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 0.5 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in Erosion as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist | Week 4, n=6, 12 | 0.3 Scores on a scale | Standard Error 0.3 |
| GSK3196165 180 mg | Change From Baseline in Erosion as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist | Week 12, n=5, 21 | 0.4 Scores on a scale | Standard Error 0.26 |
| GSK3196165 180 mg | Change From Baseline in Erosion 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 0.27 |
Comparison: Week 4p-value: 0.94595% CI: [-1.1, 1.2]Repeated measures analysis
Comparison: Week 12p-value: 0.47595% CI: [-1.5, 0.7]Repeated measures analysis
Comparison: 12-Week FUp-value: 0.08695% CI: [-2, 0.1]Repeated measures analysis
Secondary
Change From Baseline in Erosion as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist
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).
Time frame: Baseline and Weeks 4, 12 and 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in Erosion as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist | Week 4, n=6, 12 | 0.0006 Milliliters | Standard Error 0.0008 |
| GSK3196165 180 mg | Change From Baseline in Erosion as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist | Week 12, n=5, 21 | -0.0000 Milliliters | Standard Error 0.0006 |
| GSK3196165 180 mg | Change From Baseline in Erosion as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist | 12-Week FU, n=7, 19 | 0.0003 Milliliters | Standard Error 0.0013 |
Comparison: Week 4p-value: 0.91595% CI: [-0.0033, 0.0029]Repeated measures analysis
Comparison: Week 12p-value: 0.77195% CI: [-0.0028, 0.0021]Repeated measures analysis
Comparison: 12-Week FUp-value: 0.8595% CI: [-0.0048, 0.0058]Repeated measures analysis
Secondary
Change From Baseline in Osteitis as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist
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).
Time frame: Baseline and Weeks 4, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | 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 0.06 |
| GSK3196165 180 mg | Change From Baseline in Osteitis 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 0.56 |
| GSK3196165 180 mg | Change From Baseline in Osteitis as Assessed by OMERACT RAMRI Scoring System in the Most Affected Hand/Wrist | 12-Week FU, n=7,19 | -0.9 Scores on a scale | Standard Error 0.74 |
Comparison: Week 4p-value: 0.9495% CI: [-0.2, 0.3]Repeated measures analysis
Comparison: Week 12p-value: 0.52195% CI: [-3.2, 1.6]Repeated measures analysis
Comparison: 12-Week FUp-value: 0.39695% CI: [-4.4, 1.8]Repeated measures analysis
Secondary
Change From Baseline in Osteitis as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist
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).
Time frame: Baseline and Weeks 4, 12 and 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | Change From Baseline in Osteitis as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist | Week 4, n=6, 12 | 0.0084 Milliliters | Standard Error 0.0057 |
| GSK3196165 180 mg | Change From Baseline in Osteitis as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist | Week 12, n=5, 21 | -0.0009 Milliliters | Standard Error 0.0019 |
| GSK3196165 180 mg | Change From Baseline in Osteitis as Assessed by RAMRIQ Assessment in the Most Affected Hand/Wrist | 12-Week FU, n=7, 19 | -0.0027 Milliliters | Standard Error 0.0009 |
Comparison: Week 4p-value: 0.29195% CI: [-0.0123, 0.038]Repeated measures analysis
Comparison: Week 12p-value: 0.37595% CI: [-0.0046, 0.0118]Repeated measures analysis
Comparison: 12-Week FUp-value: 0.58895% CI: [-0.0028, 0.0049]Repeated measures analysis
Secondary
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
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).
Time frame: Baseline and Weeks 4, 12, 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3196165 180 mg | 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 | -0.07 Scores on a scale |
| GSK3196165 180 mg | 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 | -1.33 Scores on a scale |
| GSK3196165 180 mg | 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 |
Comparison: Week 4, For Posterior Probability Difference \<0p-value: 0.54795% CI: [-2.32, 2.23]Repeated Measures Bayesian Model
Comparison: Week 12, For Posterior Probability Difference \<0p-value: 0.94895% CI: [-4.77, 0.51]Repeated Measures Bayesian Model
Comparison: 12-Week FU, For Posterior Probability Difference \<0p-value: 0.94995% CI: [-5.02, 0.45]Repeated Measures Bayesian Model
Comparison: Week 4, For Posterior Probability Difference \>0p-value: 0.45395% CI: [-2.32, 2.23]Repeated Measures Bayesian Model
Comparison: Week 12, For Posterior Probability Difference \>0p-value: 0.05295% CI: [-4.77, 0.51]Repeated Measures Bayesian Model
Comparison: 12-Week FU, For Posterior Probability Difference \>0p-value: 0.05195% CI: [-5.02, 0.45]Repeated Measures Bayesian Model
Secondary
Change From Baseline in Synovitis as Assessed by Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Assessment in the Most Affected Hand/Wrist
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).
Time frame: Baseline and Weeks 4, 12 and 12-Week FU (Week 22)
Population: ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 1372.2 |
| GSK3196165 180 mg | 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 | 245.5 Milliliters | Standard Error 776.24 |
| GSK3196165 180 mg | 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 | -1417.0 Milliliters | Standard Error 671.54 |
| GSK3196165 180 mg | 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 | -1172.1 Milliliters | Standard Error 844.13 |
Comparison: 12-Week FUp-value: 0.35295% CI: [-4884.2, 1812.1]Repeated measures analysis
Comparison: Week 4p-value: 0.87495% CI: [-2589.2, 3012]Repeated measures analysis
Comparison: Week 12p-value: 0.74995% CI: [-3730.4, 2720.9]Repeated measures analysis
Secondary
Number of Participants Who Tested Positive for Anti-GSK3196165 Binding Antibody Detection at Any Time Post-Baseline
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.
Time frame: Up to 12-Week FU (Week 22)
Population: Immunogenicity Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Tested Positive for Anti-GSK3196165 Binding Antibody Detection at Any Time Post-Baseline | 0 Participants |
| GSK3196165 180 mg | Number of Participants Who Tested Positive for Anti-GSK3196165 Binding Antibody Detection at Any Time Post-Baseline | 0 Participants |
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)
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.
Time frame: Up to 12-Week FU (Week 22)
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Any AEs | 4 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Any SAEs | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | AESI | 0 Participants |
| GSK3196165 180 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Any AEs | 11 Participants |
| GSK3196165 180 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Any SAEs | 0 Participants |
| GSK3196165 180 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | AESI | 1 Participants |