Osteoarthritis
Conditions
Keywords
Pain intensity, Hand Osteoarthritis, GSK3196165, AUSCAN, GM-CSF, Numerical Rating Scale
Brief summary
This is a randomized, Phase IIa, multicentre, double-blind, placebo-controlled parallel group study with the primary objective to assess the efficacy potential of GSK3196165 on pain, in subjects with active inflammatory hand osteoarthritis (HOA). Approximately 40 subjects will be enrolled into the study, following a screening period of up to 4 weeks. The total treatment period will be 12 weeks, with the follow up period completing at Week 22. At least 40 subjects will be randomized across the two treatment arms, to either placebo or GSK3196165 in a 1:1 ratio.
Interventions
DRUGGSK3196165
GSK3196165 will be supplied as a liquid and will be administered as a subcutaneous injection. The drug will be administered weekly for 5 injections, then every other week for 3 further injections.
DRUGPlacebo
Matching placebo will be administered as above.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, 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) classification of osteoarthritis (OA) and have not responded to analgesics (level 1 and 2) or to non-steroidal anti-inflammatory drugs (NSAIDs) for at least 10 days in the past 3 months. * Active disease at screening and randomization with at least two swollen and tender proximal interphalangeal (PIP) and/or distal interphalangeal (DIP) joints in the affected hand. * Signs of inflammation such as synovitis in the MRI scan of the affected hand. * Must have a subject's self assessment of 24-hour average hand pain intensity at baseline of at least '5' on an 11-point Numerical Rating Scale (NRS, 0-10). * Weight \>=45 kilogram (kg). * Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria. * Diffusing capacity of the lung for carbon monoxide (DLCO) \>=70% predicted; forced expiratory volume in 1 second (FEV1) \>=80% predicted. * No evidence of active or latent infection with Mycobacterium tuberculosis (TB).
Exclusion criteria
* Pregnant or lactating women. * History of any clinically significant inflammatory disease other than inflammatory HOA, especially, but not limited to, rheumatoid arthritis or spondylarthropathies. * Diagnosis of rheumatoid arthritis, fibromyalgia, gout, calcium pyrophosphate deposition disease (CPPD), pseudogout, hemochromatosis or other inflammatory rheumatological or autoimmune disorders. * Clinical suspicion of, or previous investigation for CPPD or pseudogout, or history of chondrocalcinosis. * Any injury, medical or surgical procedure to the affected joint(s) that may interfere with evaluation of the target HOA joint(s). * History of infected joint prosthesis at any time, with the prosthesis still in situ. History of leg ulcers, catheters, chronic sinusitis or recurrent chest or urinary tract infections. * Any surgical procedure, including bone or joint surgery/synovectomy within 12 weeks prior to Day 1 or any planned surgery within the duration of the study or follow-up period. * 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 or unstable (in the opinion of the investigator) persistent cough or 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. * Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency. * 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 24-hour Average Hand Pain Intensity, Averaged Over the 7 Days Prior to Week 6 | Baseline (Day 1 Pre-dose) and Week 6 | Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors 0 (no pain) and 10 (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score was calculated as sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value. Intent-To-Treat Population comprised of all randomized participants who received at least one dose of study treatment (GSK3196165 or placebo). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12 | Participants were required to complete a daily pain NRS based on their 24-hour worst hand pain intensity with the anchors 0 (no pain) and 10 (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The score is calculated as sum of daily 24 hours worst hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value. |
| Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22) | Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 30 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is reported. |
| Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22) | Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 50 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented. |
| Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22) | Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 30 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented. |
| Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22) | Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 50 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented. |
| Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12 | The AUSCAN Index is a self-administered questionnaire consisting of a 15-item scale which measures pain (5 items), stiffness (1 item) and degree of disability/physical function (9 items) during the preceding 48 hours. All items are rated on NRS scale with anchors 0 (none) to 10 (extreme). The scores for the pain and physical function components were calculated as simple summation of the item scores relating to that domain, so the Pain component ranges from 0 (i.e. all pain item scores are scored 0 \[none\]) to 50 (i.e. all pain item scores are scored 10 \[extreme\]), and the Physical Function component ranges from 0 (i.e. all physical function item scores are scored 0 \[none\]) to 90 (i.e. all physical function item scores are scored 10 \[extreme\]). The total AUSCAN score was calculated as simple summation of the 15 item scores and therefore ranges from 0 to 150. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value. |
| Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12 | Swollen Hand Joint Count was measured by the total number of soft tissue swollen hand joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joint across both hands. In case of missing observations for soft tissue swollen hand joints then the remaining observations were assessed and weighted by dividing the number presented by the number of non-missing, and by multiplying by 30 for the joint count. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value. |
| Change From Baseline in Number of Tender Hand Joints at Each Visit | Baseline, Weeks 1, 2, 4, 6, 8, 10, and 12 | Tender Hand Joint Count was measured by the total number of tender joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joints across both hands. A joint was considered tender if it was scored \>0 on the tender joint severity scale. Joints were rated 0=no pain/tenderness, 1=mild pain, 2=moderate pain and 3=severe pain. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value. |
| Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity | Baseline (Day 1 Pre-dose), Weeks 2, 4, 8, and 12 | Physicians were required to complete the global assessment of disease activity using single PhGA item with a NRS ranging from 0 (none) to 10 (extremely active). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value. |
| Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12 | Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors 0 (no pain) and 10 (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score is calculated by sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value. |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Up to Week 22 | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who received at least one dose of study treatment (GSK3196165 or placebo) were included in Safety Population. |
| Number of Participants With Infections | Up to Week 22 | Adverse events of special interest (AESI) included serious infections like serious respiratory infections and tuberculosis and other opportunistic infections. Number of participants with infections has been reported. |
| Number of Participants With Pulmonary Events | Up to Week 22 | Pulmonary events like pulmonary alveolar proteinosis (PAP), persistent (for 3 consecutive weeks) reduction in diffusing capacity of the lungs for carbon monoxide (DLCO) \> 15 percentage, persistent (for 3 consecutive weeks) cough and/or dyspnea and non- life threatening pulmonary changes related to surfactant accumulation is presented. |
| Number of Participants With Anti-GSK3196165 Binding Antibodies | Up to Week 22 | Serum samples were collected at indicated time points for anti-drug antibody (ADA) measurements. Anti-GSK3196165 binding antibody detection assay using tiered testing schema: screening, confirmation and titration steps was used for immunogenicity analysis. Samples taken after dosing with GSK3196165 that have a value at or above the cut-point were considered treatment-emergent ADA-positive. The number of participants with change from Baseline to any time post Baseline in the results of immunogenicity assessment as indicated by: negative to positive, positive to positive, positive to negative and negative to negative are presented. |
| Apparent Clearance After Subcutaneous Administration (CL/F) of GSK3196165 | Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22 | Blood samples were collected at indicated time points and CL/F was estimated using population PK analysis. Participants in the 'Safety' population who have at least one valid PK assessment were included Pharmacokinetic (PK) Population. |
| Apparent Steady State Volume of Distribution After Subcutaneous Administration (Vss/F) of GSK3196165 | Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22 | Blood samples were collected at indicated time points and Vss/F was estimated using population PK analysis. |
| Absoption Rate Constant (Ka) of GSK3196165 | Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22 | Blood samples were collected at indicated time points and Ka was estimated using population PK analysis. |
| Serum Concentration of GSK3196165 by Visit | Pre-dose on Day 3, Weeks 1, 4, 6, 12, follow up (Week 22) | Blood samples were collected at indicated time points for pharmacokinetic analysis. |
| Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity | Baseline, Weeks 2, 4, 8, and 12 | Participants were required to complete the global assessment of disease activity using single PtGA item with an NRS ranging from 0 (very well) to 10 (very poor). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value. |
Countries
Germany, Netherlands, Poland, United Kingdom, United States
Participant flow
Recruitment details
This was a multi-center, double-blind, placebo-controlled study to investigate the efficacy and safety of GSK3196165 in participants with inflammatory hand osteoarthritis. The study was conducted in five countries in Poland, United Kingdom, Netherlands, Germany and United States.
Pre-assignment details
A total 121 participants were screened of which 77 were screen failures and 44 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to Placebo group received total of 8 subcutaneous injections of placebo over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71). | 22 |
| GSK3196165 180mg Participants randomized to GSK3196165 group received total of 8 doses of GSK3196165 over a 12-week treatment period. Participants were administered loading doses on Days 1, 8, 15, 22 and 29 which was followed by 3 doses every other week (Days 43, 57, 71). | 22 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | GSK3196165 180mg | Total |
|---|---|---|---|
| Age, Continuous | 56.7 Years STANDARD_DEVIATION 6.8 | 60.9 Years STANDARD_DEVIATION 6.25 | 58.8 Years STANDARD_DEVIATION 6.79 |
| Race/Ethnicity, Customized White - White /Caucasian/European | 22 Participants | 22 Participants | 44 Participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 4 / 22 | 10 / 22 |
| serious Total, serious adverse events | 1 / 22 | 2 / 22 |
Outcome results
Primary
Change From Baseline in 24-hour Average Hand Pain Intensity, Averaged Over the 7 Days Prior to Week 6
Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors 0 (no pain) and 10 (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score was calculated as sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value. Intent-To-Treat Population comprised of all randomized participants who received at least one dose of study treatment (GSK3196165 or placebo).
Time frame: Baseline (Day 1 Pre-dose) and Week 6
Population: Intent To Treat Population. Only non-missing data is included MMRM model.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in 24-hour Average Hand Pain Intensity, Averaged Over the 7 Days Prior to Week 6 | -1.34 Scores on scale | Standard Error 0.325 |
| GSK3196165 180mg | Change From Baseline in 24-hour Average Hand Pain Intensity, Averaged Over the 7 Days Prior to Week 6 | -1.70 Scores on scale | Standard Error 0.334 |
p-value: 0.44295% CI: [-1.31, 0.58]Mixed Model Repeated Measures Analysis
Secondary
Absoption Rate Constant (Ka) of GSK3196165
Blood samples were collected at indicated time points and Ka was estimated using population PK analysis.
Time frame: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absoption Rate Constant (Ka) of GSK3196165 | 0.205 Per day | Geometric Coefficient of Variation 72.3 |
Secondary
Apparent Clearance After Subcutaneous Administration (CL/F) of GSK3196165
Blood samples were collected at indicated time points and CL/F was estimated using population PK analysis. Participants in the 'Safety' population who have at least one valid PK assessment were included Pharmacokinetic (PK) Population.
Time frame: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Clearance After Subcutaneous Administration (CL/F) of GSK3196165 | 4.94 Liters per day | Geometric Coefficient of Variation 68.8 |
Secondary
Apparent Steady State Volume of Distribution After Subcutaneous Administration (Vss/F) of GSK3196165
Blood samples were collected at indicated time points and Vss/F was estimated using population PK analysis.
Time frame: Day 3 and Pre-dose on Week 1, Week 4, Week 6, Week 12 and Week 22
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Steady State Volume of Distribution After Subcutaneous Administration (Vss/F) of GSK3196165 | 36.5 Liters | Geometric Coefficient of Variation 61.5 |
Secondary
Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit
Participants were required to complete a daily pain NRS based on their 24-hour average hand pain intensity with the anchors 0 (no pain) and 10 (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The 7 day average score is calculated by sum of daily 24 hours average hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value.
Time frame: Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Population: Intent To Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 1, n=22, 20 | -0.13 Scores on scale | Standard Error 0.152 |
| Placebo | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 6, n=21, 20 | -1.34 Scores on scale | Standard Error 0.325 |
| Placebo | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 3, n=21, 20 | -0.74 Scores on scale | Standard Error 0.279 |
| Placebo | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 8, n=20, 19 | -1.27 Scores on scale | Standard Error 0.382 |
| Placebo | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 10, n=20, 19 | -1.18 Scores on scale | Standard Error 0.376 |
| Placebo | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 2, n=21, 20 | -0.48 Scores on scale | Standard Error 0.23 |
| Placebo | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 12, n=19, 18 | -1.35 Scores on scale | Standard Error 0.402 |
| Placebo | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 4, n=21, 20 | -0.91 Scores on scale | Standard Error 0.291 |
| GSK3196165 180mg | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 12, n=19, 18 | -2.24 Scores on scale | Standard Error 0.416 |
| GSK3196165 180mg | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 1, n=22, 20 | -0.59 Scores on scale | Standard Error 0.16 |
| GSK3196165 180mg | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 2, n=21, 20 | -0.86 Scores on scale | Standard Error 0.239 |
| GSK3196165 180mg | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 3, n=21, 20 | -1.24 Scores on scale | Standard Error 0.289 |
| GSK3196165 180mg | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 4, n=21, 20 | -1.65 Scores on scale | Standard Error 0.301 |
| GSK3196165 180mg | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 6, n=21, 20 | -1.70 Scores on scale | Standard Error 0.334 |
| GSK3196165 180mg | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 10, n=20, 19 | -2.09 Scores on scale | Standard Error 0.389 |
| GSK3196165 180mg | Change From Baseline in 24 Hours Average Hand Pain Intensity Averaged Over the 7 Days Prior to Each Visit | Week 8, n=20, 19 | -2.10 Scores on scale | Standard Error 0.393 |
p-value: 0.04695% CI: [-0.9, -0.01]Mixed Model Repeated Measures Analysis
p-value: 0.25795% CI: [-1.05, 0.29]Mixed Model Repeated Measures Analysis
p-value: 0.2295% CI: [-1.31, 0.31]Mixed Model Repeated Measures Analysis
p-value: 0.08595% CI: [-1.59, 0.11]Mixed Model Repeated Measures Analysis
p-value: 0.44295% CI: [-1.31, 0.58]Mixed Model Repeated Measures Analysis
p-value: 0.13995% CI: [-1.93, 0.28]Mixed Model Repeated Measures Analysis
p-value: 0.10395% CI: [-2, 0.19]Mixed Model Repeated Measures Analysis
p-value: 0.13295% CI: [-2.06, 0.28]Mixed Model Repeated Measures Analysis
Secondary
Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit.
The AUSCAN Index is a self-administered questionnaire consisting of a 15-item scale which measures pain (5 items), stiffness (1 item) and degree of disability/physical function (9 items) during the preceding 48 hours. All items are rated on NRS scale with anchors 0 (none) to 10 (extreme). The scores for the pain and physical function components were calculated as simple summation of the item scores relating to that domain, so the Pain component ranges from 0 (i.e. all pain item scores are scored 0 \[none\]) to 50 (i.e. all pain item scores are scored 10 \[extreme\]), and the Physical Function component ranges from 0 (i.e. all physical function item scores are scored 0 \[none\]) to 90 (i.e. all physical function item scores are scored 10 \[extreme\]). The total AUSCAN score was calculated as simple summation of the 15 item scores and therefore ranges from 0 to 150. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12
Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 8, n=20, 20 | -8.3 Scores on scale | Standard Error 3.57 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 12, n=21, 19 | -4.6 Scores on scale | Standard Error 1.84 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 12, n=21, 19 | -7.2 Scores on scale | Standard Error 3.74 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 4, n= 22, 21 | -11.4 Scores on scale | Standard Error 4.72 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 1, n=22, 20 | 0.8 Scores on scale | Standard Error 0.98 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 2, n=21, 21 | -1.8 Scores on scale | Standard Error 1.27 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 6, n=22, 21 | -6.6 Scores on scale | Standard Error 1.72 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 8, n=20, 20 | -4.9 Scores on scale | Standard Error 1.93 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 10, n=20, 20 | -5.3 Scores on scale | Standard Error 1.82 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 1, n= 22, 20 | -0.4 Scores on scale | Standard Error 0.29 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 2, n= 21, 21 | -0.8 Scores on scale | Standard Error 0.33 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 4, n= 22, 21 | -1.2 Scores on scale | Standard Error 0.41 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 6, n= 22, 21 | -1.4 Scores on scale | Standard Error 0.39 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 8, n= 20, 20 | -1.2 Scores on scale | Standard Error 0.41 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 10, n= 20, 20 | -1.6 Scores on scale | Standard Error 0.44 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 12, n= 21, 19 | -1.5 Scores on scale | Standard Error 0.45 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 1, n=22, 20 | -0.7 Scores on scale | Standard Error 2.08 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 2, n=21,21 | -2.8 Scores on scale | Standard Error 2.35 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 4, n=22, 21 | -6.4 Scores on scale | Standard Error 3.01 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 6, n=22, 21 | -9.1 Scores on scale | Standard Error 3.25 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 4, n=22, 21 | -3.5 Scores on scale | Standard Error 1.61 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 10, n=20, 20 | -9.0 Scores on scale | Standard Error 3.82 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 1, n= 22, 20 | -0.5 Scores on scale | Standard Error 3.07 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 2, n= 21, 21 | -5.7 Scores on scale | Standard Error 3.66 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 6, n= 22, 21 | -17.3 Scores on scale | Standard Error 5.17 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 8, n= 20, 20 | -14.6 Scores on scale | Standard Error 5.7 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 10, n= 20, 20 | -16.1 Scores on scale | Standard Error 5.88 |
| Placebo | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 12, n= 21, 19 | -13.5 Scores on scale | Standard Error 5.92 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 12, n= 21, 19 | -26.7 Scores on scale | Standard Error 6.12 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 8, n=20, 20 | -8.7 Scores on scale | Standard Error 1.97 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 10, n=20, 20 | -10.9 Scores on scale | Standard Error 1.87 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 8, n= 20, 20 | -1.9 Scores on scale | Standard Error 0.42 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 12, n=21, 19 | -9.3 Scores on scale | Standard Error 1.91 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 10, n= 20, 20 | -2.2 Scores on scale | Standard Error 0.45 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 8, n=20, 20 | -13.2 Scores on scale | Standard Error 3.64 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 12, n=21, 19 | -15.4 Scores on scale | Standard Error 3.87 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 2, n= 21, 21 | -10.4 Scores on scale | Standard Error 3.7 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 6, n= 22, 21 | -20.7 Scores on scale | Standard Error 5.28 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 4, n= 22, 21 | -20.1 Scores on scale | Standard Error 4.83 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 12, n= 21, 19 | -2.2 Scores on scale | Standard Error 0.47 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 1, n=22, 20 | -1.9 Scores on scale | Standard Error 1.03 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 10, n=20, 20 | -15.2 Scores on scale | Standard Error 3.92 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 2, n=21, 21 | -3.7 Scores on scale | Standard Error 1.28 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 4, n=22, 21 | -7.2 Scores on scale | Standard Error 1.64 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 1, n=22, 20 | -3.6 Scores on scale | Standard Error 2.16 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Pain, Week 6, n=22, 21 | -7.6 Scores on scale | Standard Error 1.76 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 10, n= 20, 20 | -28.2 Scores on scale | Standard Error 6.04 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 2, n=21,21 | -5.7 Scores on scale | Standard Error 2.37 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 1, n= 22, 20 | -6.0 Scores on scale | Standard Error 3.2 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 1, n= 22, 20 | -0.6 Scores on scale | Standard Error 0.31 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 4, n=22, 21 | -11.3 Scores on scale | Standard Error 3.07 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 2, n= 21, 21 | -1.1 Scores on scale | Standard Error 0.33 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Total, Week 8, n= 20, 20 | -23.6 Scores on scale | Standard Error 5.81 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 4, n= 22, 21 | -1.8 Scores on scale | Standard Error 0.42 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Physical function, Week 6, n=22, 21 | -11.8 Scores on scale | Standard Error 3.32 |
| GSK3196165 180mg | Change From Baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS Scores at Each Visit. | Stiffness, Week 6, n= 22, 21 | -1.6 Scores on scale | Standard Error 0.4 |
p-value: 0.06195% CI: [-5.6, 0.1]Mixed Model Repeated Measures Analysis
p-value: 0.28295% CI: [-5.6, 1.7]Mixed Model Repeated Measures Analysis
p-value: 0.11395% CI: [-8.4, 0.9]Mixed Model Repeated Measures Analysis
p-value: 0.69595% CI: [-5.9, 4]Mixed Model Repeated Measures Analysis
p-value: 0.17695% CI: [-9.4, 1.8]Mixed Model Repeated Measures Analysis
p-value: 0.04195% CI: [-10.8, -0.2]Mixed Model Repeated Measures Analysis
p-value: 0.08295% CI: [-10.1, 0.6]Mixed Model Repeated Measures Analysis
p-value: 0.58795% CI: [-1.1, 0.6]Mixed Model Repeated Measures Analysis
p-value: 0.45795% CI: [-1.3, 0.6]Mixed Model Repeated Measures Analysis
p-value: 0.29895% CI: [-1.8, 0.6]Mixed Model Repeated Measures Analysis
p-value: 0.72695% CI: [-1.3, 0.9]Mixed Model Repeated Measures Analysis
p-value: 0.21395% CI: [-1.9, 0.4]Mixed Model Repeated Measures Analysis
p-value: 0.33195% CI: [-1.9, 0.7]Mixed Model Repeated Measures Analysis
p-value: 0.24895% CI: [-2.1, 0.6]Mixed Model Repeated Measures Analysis
p-value: 0.3595% CI: [-9, 3.3]Mixed Model Repeated Measures Analysis
p-value: 0.38395% CI: [-9.8, 3.8]Mixed Model Repeated Measures Analysis
p-value: 0.27195% CI: [-13.5, 3.9]Mixed Model Repeated Measures Analysis
p-value: 0.56595% CI: [-12.1, 6.7]Mixed Model Repeated Measures Analysis
p-value: 0.34395% CI: [-15.2, 5.4]Mixed Model Repeated Measures Analysis
p-value: 0.26695% CI: [-17.3, 4.9]Mixed Model Repeated Measures Analysis
p-value: 0.13695% CI: [-19.1, 2.7]Mixed Model Repeated Measures Analysis
p-value: 0.2395% CI: [-14.5, 3.6]Mixed Model Repeated Measures Analysis
p-value: 0.38195% CI: [-15.2, 5.9]Mixed Model Repeated Measures Analysis
p-value: 0.20795% CI: [-22.4, 5]Mixed Model Repeated Measures Analysis
p-value: 0.64895% CI: [-18.4, 11.6]Mixed Model Repeated Measures Analysis
p-value: 0.27895% CI: [-25.4, 7.5]Mixed Model Repeated Measures Analysis
p-value: 0.1695% CI: [-29.1, 5]Mixed Model Repeated Measures Analysis
p-value: 0.12795% CI: [-30.5, 3.9]Mixed Model Repeated Measures Analysis
Secondary
Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit
Swollen Hand Joint Count was measured by the total number of soft tissue swollen hand joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joint across both hands. In case of missing observations for soft tissue swollen hand joints then the remaining observations were assessed and weighted by dividing the number presented by the number of non-missing, and by multiplying by 30 for the joint count. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 Pre-dose), Weeks 1, 2, 4, 6, 8, 10, and 12
Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 4, n = 22, 21 | -1.6 Swollen joints | Standard Error 0.76 |
| Placebo | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 6, n = 22, 21 | -3.7 Swollen joints | Standard Error 0.83 |
| Placebo | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 12, n = 21, 19 | -2.9 Swollen joints | Standard Error 0.91 |
| Placebo | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 8, n = 20, 20 | -3.0 Swollen joints | Standard Error 0.92 |
| Placebo | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 2, n = 21, 21 | -1.6 Swollen joints | Standard Error 0.85 |
| Placebo | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 10, n = 20, 20 | -2.6 Swollen joints | Standard Error 1.08 |
| Placebo | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 1, n = 22, 21 | -0.3 Swollen joints | Standard Error 0.64 |
| GSK3196165 180mg | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 10, n = 20, 20 | -2.9 Swollen joints | Standard Error 1.1 |
| GSK3196165 180mg | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 12, n = 21, 19 | -3.1 Swollen joints | Standard Error 0.93 |
| GSK3196165 180mg | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 1, n = 22, 21 | -0.3 Swollen joints | Standard Error 0.66 |
| GSK3196165 180mg | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 2, n = 21, 21 | -1.2 Swollen joints | Standard Error 0.86 |
| GSK3196165 180mg | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 6, n = 22, 21 | -2.3 Swollen joints | Standard Error 0.85 |
| GSK3196165 180mg | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 8, n = 20, 20 | -2.8 Swollen joints | Standard Error 0.94 |
| GSK3196165 180mg | Change From Baseline in Number of Soft Tissue Swollen Hand Joints at Each Visit | Week 4, n = 22, 21 | -2.1 Swollen joints | Standard Error 0.78 |
p-value: 0.95795% CI: [-1.9, 1.8]Mixed Model Repeated Measures Analysis
p-value: 0.77595% CI: [-2.1, 2.8]Mixed Model Repeated Measures Analysis
p-value: 0.62495% CI: [-2.7, 1.7]Mixed Model Repeated Measures Analysis
p-value: 0.24395% CI: [-1, 3.8]Mixed Model Repeated Measures Analysis
p-value: 0.87595% CI: [-2.5, 2.9]Mixed Model Repeated Measures Analysis
p-value: 0.84895% CI: [-3.4, 2.8]Mixed Model Repeated Measures Analysis
p-value: 0.88395% CI: [-2.8, 2.4]Mixed Model Repeated Measures Analysis
Secondary
Change From Baseline in Number of Tender Hand Joints at Each Visit
Tender Hand Joint Count was measured by the total number of tender joints out of a possible 30 joints: 8 distal interphalangeal, 8 proximal interphalangeal, 2 interphalangeal joints, 10 metacarpophalangeal joints, 2 carpometacarpal joints across both hands. A joint was considered tender if it was scored \>0 on the tender joint severity scale. Joints were rated 0=no pain/tenderness, 1=mild pain, 2=moderate pain and 3=severe pain. Baseline is defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
Time frame: Baseline, Weeks 1, 2, 4, 6, 8, 10, and 12
Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data was included in the MMRM model.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 8, n= 20, 20 | -2.4 Scores on scale | Standard Error 1.36 |
| Placebo | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 4, n= 22, 21 | -1.1 Scores on scale | Standard Error 1.33 |
| Placebo | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 1, n= 22, 21 | -0.6 Scores on scale | Standard Error 1.1 |
| Placebo | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 10, n= 20, 20 | -3.7 Scores on scale | Standard Error 1.45 |
| Placebo | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 6, n= 22, 21 | -3.7 Scores on scale | Standard Error 1.27 |
| Placebo | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 12, n= 21, 19 | -3.5 Scores on scale | Standard Error 1.46 |
| Placebo | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 2, n= 21, 21 | -1.7 Scores on scale | Standard Error 1.15 |
| GSK3196165 180mg | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 12, n= 21, 19 | -4.0 Scores on scale | Standard Error 1.51 |
| GSK3196165 180mg | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 6, n= 22, 21 | -4.2 Scores on scale | Standard Error 1.3 |
| GSK3196165 180mg | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 1, n= 22, 21 | -1.8 Scores on scale | Standard Error 1.13 |
| GSK3196165 180mg | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 2, n= 21, 21 | -2.1 Scores on scale | Standard Error 1.17 |
| GSK3196165 180mg | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 8, n= 20, 20 | -3.9 Scores on scale | Standard Error 1.39 |
| GSK3196165 180mg | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 10, n= 20, 20 | -4.4 Scores on scale | Standard Error 1.48 |
| GSK3196165 180mg | Change From Baseline in Number of Tender Hand Joints at Each Visit | Week 4, n= 22, 21 | -3.0 Scores on scale | Standard Error 1.36 |
p-value: 0.46395% CI: [-4.4, 2]Mixed Model Repeated Measures Analysis
p-value: 0.80995% CI: [-3.7, 2.9]Mixed Model Repeated Measures Analysis
p-value: 0.32495% CI: [-5.8, 2]Mixed Model Repeated Measures Analysis
p-value: 0.78395% CI: [-4.2, 3.2]Mixed Model Repeated Measures Analysis
p-value: 0.46495% CI: [-5.4, 2.5]Mixed Model Repeated Measures Analysis
p-value: 0.73695% CI: [-4.9, 3.5]Mixed Model Repeated Measures Analysis
p-value: 0.80695% CI: [-4.8, 3.7]Mixed Model Repeated Measures Analysis
Secondary
Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity
Participants were required to complete the global assessment of disease activity using single PtGA item with an NRS ranging from 0 (very well) to 10 (very poor). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity | Week 2, n= 20, 21 | -0.4 Scores on scale | Standard Error 0.36 |
| Placebo | Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity | Week 4, n= 21, 21 | -0.6 Scores on scale | Standard Error 0.42 |
| Placebo | Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity | Week 8, n= 19, 20 | -0.9 Scores on scale | Standard Error 0.47 |
| Placebo | Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity | Week 12, n= 20, 19 | -0.7 Scores on scale | Standard Error 0.46 |
| GSK3196165 180mg | Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity | Week 12, n= 20, 19 | -1.8 Scores on scale | Standard Error 0.46 |
| GSK3196165 180mg | Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity | Week 2, n= 20, 21 | -0.6 Scores on scale | Standard Error 0.35 |
| GSK3196165 180mg | Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity | Week 8, n= 19, 20 | -1.8 Scores on scale | Standard Error 0.46 |
| GSK3196165 180mg | Change From Baseline in Patient Global Assessment (PtGA) of Disease Activity | Week 4, n= 21, 21 | -1.3 Scores on scale | Standard Error 0.42 |
p-value: 0.65195% CI: [-1.3, 0.8]Mixed Model Repeated Measures Analysis
p-value: 0.27195% CI: [-1.9, 0.5]Mixed Model Repeated Measures Analysis
p-value: 0.18695% CI: [-2.2, 0.4]Mixed Model Repeated Measures Analysis
p-value: 0.10995% CI: [-2.4, 0.2]Mixed Model Repeated Measures Analysis
Secondary
Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity
Physicians were required to complete the global assessment of disease activity using single PhGA item with a NRS ranging from 0 (none) to 10 (extremely active). Baseline was defined as Day 1 pre-dose value. Change from Baseline is equal to post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 Pre-dose), Weeks 2, 4, 8, and 12
Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity | Week 8, n= 17, 15 | -2.2 Scores on scale | Standard Error 0.52 |
| Placebo | Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity | Week 4, n= 20, 15 | -2.1 Scores on scale | Standard Error 0.44 |
| Placebo | Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity | Week 12, n= 18, 14 | -2.7 Scores on scale | Standard Error 0.56 |
| Placebo | Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity | Week 2, n= 19, 14 | -1.8 Scores on scale | Standard Error 0.39 |
| GSK3196165 180mg | Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity | Week 12, n= 18, 14 | -3.0 Scores on scale | Standard Error 0.63 |
| GSK3196165 180mg | Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity | Week 4, n= 20, 15 | -2.6 Scores on scale | Standard Error 0.5 |
| GSK3196165 180mg | Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity | Week 8, n= 17, 15 | -3.4 Scores on scale | Standard Error 0.57 |
| GSK3196165 180mg | Change From Baseline in Physician Global Assessment (PhGA) of Disease Activity | Week 2, n= 19, 14 | -1.5 Scores on scale | Standard Error 0.45 |
p-value: 0.1295% CI: [-2.8, 0.3]Mixed Model Repeated Measures Analysis
p-value: 0.68795% CI: [-2.1, 1.4]Mixed Model Repeated Measures Analysis
p-value: 0.58695% CI: [-0.9, 1.6]Mixed Model Repeated Measures Analysis
p-value: 0.41695% CI: [-1.9, 0.8]Mixed Model Repeated Measures Analysis
Secondary
Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit
Participants were required to complete a daily pain NRS based on their 24-hour worst hand pain intensity with the anchors 0 (no pain) and 10 (worst imaginable pain), which was averaged over the 7 days prior to assessment visit. The score is calculated as sum of daily 24 hours worst hand pain NRS scores in the 7 days prior to assessment visit, divided by number of entries recorded in those 7 days. Baseline visit was at Day 1 and Baseline value was defined as the average of the 7 days prior to baseline visit (Day 1 pre-dose). Change from Baseline is equal to post-dose visit value minus Baseline value.
Time frame: Baseline (Pre-dose Day 1), Weeks 1, 2, 3, 4, 6, 8, 10 and 12
Population: Intent-to-Treat Population. n=X in category titles represents the number of participants with non-missing data at the specified time-point. Only non-missing data is included in the MMRM model.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 6, n= 21, 20 | -1.30 Scores on scale | Standard Error 0.328 |
| Placebo | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 1, n=22, 20 | 0.01 Scores on scale | Standard Error 0.174 |
| Placebo | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 2, n=21, 20 | -0.42 Scores on scale | Standard Error 0.235 |
| Placebo | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 3, n=21, 20 | -0.63 Scores on scale | Standard Error 0.269 |
| Placebo | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 4, n= 21, 20 | -0.72 Scores on scale | Standard Error 0.289 |
| Placebo | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 8, n= 20, 19 | -1.18 Scores on scale | Standard Error 0.394 |
| Placebo | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 10, n= 20, 19 | -1.15 Scores on scale | Standard Error 0.394 |
| Placebo | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 12, n= 19, 18 | -1.32 Scores on scale | Standard Error 0.415 |
| GSK3196165 180mg | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 12, n= 19, 18 | -2.34 Scores on scale | Standard Error 0.43 |
| GSK3196165 180mg | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 6, n= 21, 20 | -1.63 Scores on scale | Standard Error 0.337 |
| GSK3196165 180mg | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 4, n= 21, 20 | -1.51 Scores on scale | Standard Error 0.299 |
| GSK3196165 180mg | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 1, n=22, 20 | -0.45 Scores on scale | Standard Error 0.183 |
| GSK3196165 180mg | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 10, n= 20, 19 | -2.13 Scores on scale | Standard Error 0.407 |
| GSK3196165 180mg | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 2, n=21, 20 | -0.69 Scores on scale | Standard Error 0.245 |
| GSK3196165 180mg | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 8, n= 20, 19 | -2.11 Scores on scale | Standard Error 0.406 |
| GSK3196165 180mg | Change From Baseline of Worst Hand Pain Intensity Over 24 Hours Averaged Over the 7 Days Prior to Each Visit | Week 3, n=21, 20 | -1.23 Scores on scale | Standard Error 0.278 |
p-value: 0.08295% CI: [-0.97, 0.06]Mixed Model Repeated Measures Analysis
p-value: 0.42695% CI: [-0.96, 0.41]Mixed Model Repeated Measures Analysis
p-value: 0.12995% CI: [-1.38, 0.18]Mixed Model Repeated Measures Analysis
p-value: 0.06795% CI: [-1.63, 0.06]Mixed Model Repeated Measures Analysis
p-value: 0.49495% CI: [-1.28, 0.63]Mixed Model Repeated Measures Analysis
p-value: 0.10795% CI: [-2.08, 0.21]Mixed Model Repeated Measures Analysis
p-value: 0.09295% CI: [-2.13, 0.17]Mixed Model Repeated Measures Analysis
p-value: 0.09895% CI: [-2.22, 0.2]Mixed Model Repeated Measures Analysis
Secondary
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who received at least one dose of study treatment (GSK3196165 or placebo) were included in Safety Population.
Time frame: Up to Week 22
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAE | 1 Participants |
| Placebo | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any AE | 11 Participants |
| GSK3196165 180mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any AE | 13 Participants |
| GSK3196165 180mg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAE | 2 Participants |
Secondary
Number of Participants With Anti-GSK3196165 Binding Antibodies
Serum samples were collected at indicated time points for anti-drug antibody (ADA) measurements. Anti-GSK3196165 binding antibody detection assay using tiered testing schema: screening, confirmation and titration steps was used for immunogenicity analysis. Samples taken after dosing with GSK3196165 that have a value at or above the cut-point were considered treatment-emergent ADA-positive. The number of participants with change from Baseline to any time post Baseline in the results of immunogenicity assessment as indicated by: negative to positive, positive to positive, positive to negative and negative to negative are presented.
Time frame: Up to Week 22
Population: Intent-to-Treat Population. Only those participants with data available post-Baseline are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-GSK3196165 Binding Antibodies | Negative to positive | 0 Participants |
| Placebo | Number of Participants With Anti-GSK3196165 Binding Antibodies | Positive to positive | 0 Participants |
| Placebo | Number of Participants With Anti-GSK3196165 Binding Antibodies | Positive to negative | 0 Participants |
| Placebo | Number of Participants With Anti-GSK3196165 Binding Antibodies | Negative to negative | 22 Participants |
| GSK3196165 180mg | Number of Participants With Anti-GSK3196165 Binding Antibodies | Negative to negative | 20 Participants |
| GSK3196165 180mg | Number of Participants With Anti-GSK3196165 Binding Antibodies | Negative to positive | 1 Participants |
| GSK3196165 180mg | Number of Participants With Anti-GSK3196165 Binding Antibodies | Positive to negative | 0 Participants |
| GSK3196165 180mg | Number of Participants With Anti-GSK3196165 Binding Antibodies | Positive to positive | 0 Participants |
Secondary
Number of Participants With Infections
Adverse events of special interest (AESI) included serious infections like serious respiratory infections and tuberculosis and other opportunistic infections. Number of participants with infections has been reported.
Time frame: Up to Week 22
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Infections | Serious Infections | 0 Participants |
| Placebo | Number of Participants With Infections | Opportunistic Infections | 0 Participants |
| GSK3196165 180mg | Number of Participants With Infections | Serious Infections | 0 Participants |
| GSK3196165 180mg | Number of Participants With Infections | Opportunistic Infections | 0 Participants |
Secondary
Number of Participants With Pulmonary Events
Pulmonary events like pulmonary alveolar proteinosis (PAP), persistent (for 3 consecutive weeks) reduction in diffusing capacity of the lungs for carbon monoxide (DLCO) \> 15 percentage, persistent (for 3 consecutive weeks) cough and/or dyspnea and non- life threatening pulmonary changes related to surfactant accumulation is presented.
Time frame: Up to Week 22
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Pulmonary Events | Persistent Cough | 0 Participants |
| Placebo | Number of Participants With Pulmonary Events | Persistent decrease in DLCO | 0 Participants |
| Placebo | Number of Participants With Pulmonary Events | Abnormal Lung Auscultation | 0 Participants |
| Placebo | Number of Participants With Pulmonary Events | PAP | 0 Participants |
| Placebo | Number of Participants With Pulmonary Events | Persistent dyspnea | 0 Participants |
| GSK3196165 180mg | Number of Participants With Pulmonary Events | PAP | 0 Participants |
| GSK3196165 180mg | Number of Participants With Pulmonary Events | Persistent dyspnea | 0 Participants |
| GSK3196165 180mg | Number of Participants With Pulmonary Events | Persistent decrease in DLCO | 0 Participants |
| GSK3196165 180mg | Number of Participants With Pulmonary Events | Persistent Cough | 0 Participants |
| GSK3196165 180mg | Number of Participants With Pulmonary Events | Abnormal Lung Auscultation | 0 Participants |
Secondary
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 30 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is reported.
Time frame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
Population: Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 2 | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 8 | 18 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 4 | 14 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 10 | 18 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 3 | 5 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 12 | 23 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 6 | 23 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Follow up (Week 22) | 23 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 1 | 0 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Follow up (Week 22) | 27 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 1 | 9 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 2 | 18 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 3 | 23 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 4 | 41 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 6 | 45 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 8 | 50 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 10 | 50 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 12 | 45 Percentage of participants |
Secondary
Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 30 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.
Time frame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
Population: Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 2 | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 8 | 9 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 10 | 14 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 3 | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 12 | 14 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 6 | 9 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Follow up (Week 22) | 14 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 1 | 0 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Follow up (Week 22) | 32 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 1 | 9 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 2 | 18 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 3 | 23 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 4 | 32 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 6 | 36 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 8 | 45 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 10 | 45 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 30 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 12 | 45 Percentage of participants |
Secondary
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit
Participants were required to complete average pain NRS daily and rate the average hand pain over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants who achieved at least 50 percentage reduction from Baseline in the 24-hours average hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.
Time frame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
Population: Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 2 | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 6 | 14 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 1 | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 8 | 14 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 3 | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 10 | 9 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 12 | 14 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Follow up (Week 22) | 9 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 4 | 0 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Follow up (Week 22) | 23 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 1 | 0 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 2 | 9 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 3 | 18 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 4 | 23 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 6 | 27 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 8 | 41 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 12 | 41 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Average Hand Pain Intensity at Each Visit | Week 10 | 36 Percentage of participants |
Secondary
Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit
Participants were required to complete worst pain NRS daily and rate the hand pain at its worst over last 24 hours on a scale of 0 (no pain) to 10 (worst imaginable pain). The percentage of participants achieving at least 50 percentage reduction from Baseline in the 24-hours worst hand pain intensity as measured by daily NRS and averaged over 7 days prior to each visit is presented.
Time frame: Baseline (Pre-dose, Day 1), Weeks 1, 2, 3, 4, 6, 8, 10, 12 and follow up (Week 22)
Population: Intent-to-Treat Population. Participants with missing data at a particular visit had been assumed to be non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Follow up (Week 22) | 5 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 1 | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 2 | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 6 | 5 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 8 | 5 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 10 | 5 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 12 | 9 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 3 | 0 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 12 | 36 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Follow up (Week 22) | 23 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 6 | 18 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 1 | 0 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 10 | 27 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 2 | 5 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 3 | 14 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 8 | 32 Percentage of participants |
| GSK3196165 180mg | Percentage of Participants Achieving a 50 Percentage Reduction From Baseline in 24 Hours Worst Hand Pain Intensity at Each Visit | Week 4 | 18 Percentage of participants |
Secondary
Serum Concentration of GSK3196165 by Visit
Blood samples were collected at indicated time points for pharmacokinetic analysis.
Time frame: Pre-dose on Day 3, Weeks 1, 4, 6, 12, follow up (Week 22)
Population: PK Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentration of GSK3196165 by Visit | Day 3, n= 18 | 2457.05 Nanogram per milliliter | Geometric Coefficient of Variation 94.74 |
| Placebo | Serum Concentration of GSK3196165 by Visit | Week 1, n= 21 | 1767.55 Nanogram per milliliter | Geometric Coefficient of Variation 46.96 |
| Placebo | Serum Concentration of GSK3196165 by Visit | Week 4, n= 21 | 2821.12 Nanogram per milliliter | Geometric Coefficient of Variation 61 |
| Placebo | Serum Concentration of GSK3196165 by Visit | Week 6, n= 20 | 1802.09 Nanogram per milliliter | Geometric Coefficient of Variation 60.42 |
| Placebo | Serum Concentration of GSK3196165 by Visit | Week 12, n= 8 | 800.96 Nanogram per milliliter | Geometric Coefficient of Variation 176.33 |
| Placebo | Serum Concentration of GSK3196165 by Visit | Follow up (Week 22), n= 12 | 56.40 Nanogram per milliliter | Geometric Coefficient of Variation 346.41 |