Study to Evaluate the Efficacy and Safety of GSK3196165 Plus Methotrexate in Subjects With Active Moderate-Severe Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT02504671

Recruitment Status : Completed

First Posted : July 22, 2015

Results First Posted : April 4, 2019

Last Update Posted : January 11, 2021

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

GlaxoSmithKline

Study Description

Brief Summary:

This is a randomised, Phase IIb, dose-adaptive, multicentre, double-blind, parallel group, placebo-controlled study with the primary objective to assess the efficacy of GSK3196165, in combination with methotrexate (MTX), in subjects with active moderate severe rheumatoid arthritis (RA) despite treatment with MTX. Approximately 210 subjects will be randomised into the study, following a screening period of up to four weeks. The total treatment period is up to 52 weeks, with a 12-week follow-up period after the last dose (Week 50). Subjects will be randomised (1:1:1:1:1:1) to placebo or one of five subcutaneous (SC) GSK3196165 doses, in combination with MTX (at a weekly dose between 15-25 milligram [mg]), previously received for at least 12 weeks, with a stable and tolerated dose and route of administration for >=4 weeks. Escape therapy is provided at specified timepoints in the protocol for subjects that do not achieve adequate disease improvement.

Condition or disease	Intervention/treatment	Phase
Arthritis, Rheumatoid	Drug: GSK3196165 Drug: MTX Drug: Folic acid Drug: Placebo	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	222 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Phase IIb, Double-Blind, Placebo-Controlled, Dose-Adaptive, Study of the Efficacy and Safety of GSK3196165 in Combination With Methotrexate Therapy, in Subjects With Active Moderate-Severe Rheumatoid Arthritis Despite Treatment With Methotrexate
Actual Study Start Date :	July 23, 2015
Actual Primary Completion Date :	December 22, 2017
Actual Study Completion Date :	December 29, 2017

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Rheumatoid arthritis

MedlinePlus related topics: Arthritis Rheumatoid Arthritis

Drug Information available for: Folic acid

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: GSK3196165, Dose 1 + MTX and Folic acid Subject will receive GSK3196165 Dose 1 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.	Drug: GSK3196165 GSK3196165 is supplied as liquid and will be administered as SC injection. Drug: MTX MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection. Drug: Folic acid Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.
Experimental: GSK3196165, Dose 2 + MTX and folic acid Subject will receive GSK3196165 Dose 2 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.	Drug: GSK3196165 GSK3196165 is supplied as liquid and will be administered as SC injection. Drug: MTX MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection. Drug: Folic acid Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.
Experimental: GSK3196165, Dose 3 + MTX and folic acid Subject will receive GSK3196165 Dose 3 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.	Drug: GSK3196165 GSK3196165 is supplied as liquid and will be administered as SC injection. Drug: MTX MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection. Drug: Folic acid Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.
Experimental: GSK3196165, Dose 4 + MTX and folic acid Subject will receive GSK3196165 Dose 4 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.	Drug: GSK3196165 GSK3196165 is supplied as liquid and will be administered as SC injection. Drug: MTX MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection. Drug: Folic acid Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.
Experimental: GSK3196165, Dose 5 + MTX and folic acid Subject will receive GSK3196165 Dose 5 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.	Drug: GSK3196165 GSK3196165 is supplied as liquid and will be administered as SC injection. Drug: MTX MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection. Drug: Folic acid Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.
Placebo Comparator: Placebo + MTX and folic acid Subjects will receive placebo (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.	Drug: MTX MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection. Drug: Folic acid Folic acid will be supplied as capsule, tablet or liquid and will be administered orally. Drug: Placebo Placebo is supplied as liquid as sterile 0.9% weight by volume (w/v) sodium chloride solution and will be administered as SC injection

Outcome Measures

Primary Outcome Measures :

Percentage of Participants Who Achieved Disease Activity Score for 28 Different Joints With C-reactive Protein Value (DAS28{CRP}) Remission (DAS28 <2.6) at Week 24 [ Time Frame: Week 24 ]
DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 millimeter [mm] visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in [milligrams/liter] mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). ITT population comprised of all participants who were randomized to treatment and who received at least one dose of study treatment (GSK3196165 or placebo).

Secondary Outcome Measures :

Change From Baseline in DAS28(CRP) at Week 12 [ Time Frame: Baseline and Week 12 ]
DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant global assessment of disease activity (PtGA) using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
Percentage of Participants Who Achieved DAS28(CRP) Remission (DAS28 <2.6) at All Time Points [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up) ]
DAS28(CRP) remission is defined as a DAS28 score of <2.6 points. The DAS index combines information relating to the number of swollen and tender joints. The DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome).
Change From Baseline in DAS28(CRP) at All Assessment Time Points [ Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24 ]
DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline.
Time to First DAS28(CRP) Remission [ Time Frame: Up to Week 62 ]
The DAS index combines information relating to the number of swollen and tender joints. The DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). Median time, to remission has been presented.
Percentage of Participants Achieving Categorical DAS28(CRP) Response (Moderate/Good [European League Against Rheumatism] EULAR Response) at All Assessment Time Points [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up) ]
DAS28(CRP) scores were categorized using EULAR response criteria. Response at a given time point was defined based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to Baseline. The definition of no response, moderate response and good response was as follows: Current DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2=good response), (>0.6 to <=1.2 = moderate response) and (<=0.6 =no response). Current DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline value (>1.2 =moderate response), (>0.6 to <=1.2 = moderate response) and (<=0.6 =no response). Current DAS28 >5.1 and DAS28 decrease from Baseline value (>1.2=moderate response), (>0.6 to <=1.2 = no response) and (<=0.6 =no response). If the post-Baseline DAS28(CRP) score was missing, then the corresponding EULAR category was set to missing.
Percentage of Participants With American College of Rheumatology's (ACR) 20/50/70 Response Rates at All Assessment Time Points [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up) ]
The ACR definition for calculating improvement in rheumatoid arthritis is calculated as a 20% improvement (ACR20) in both tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR-core set measures: participant and physician global assessments, participant's assessment of arthritis pain, disability, and an acute-phase reactant (i.e. CRP value). Similarly, ACR50 and ACR70 were calculated with the respective percent improvement. The specific components of the ACR assessments are as follows: Tender/Painful Joint count 68 (TJC68), Swollen Joint Count 66 (SJC66), Participant's Assessment of Arthritis Pain, Participant's Global Assessment of Arthritis Disease Activity, Physician's Global Assessment of Arthritis, CRP (mg/L) and Health Assessment Questionnaire - Disability Index (HAQ-DI). For all visits, if any of the component scores were missing, then those scores were considered as not having met the criteria for improvement.
Percentage of Participants With Index-based ACR/EULAR Remission Rates at All Assessment Time Points [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up) ]
Index-based remission was achieved if the following requirement was met: SDAI <= 3.3. If the SDAI value was missing at an individual assessment point, Index-based remission for that assessment was set to missing.
Percentage of Participants With Boolean-based ACR/EULAR Remission Rates at All Assessment Time Points [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up) ]
Boolean-based remission was achieved if all of the following requirements were met at the same time: TJC68 <= 1,SJC66 <= 1,CRP <= 1mg/dL, PtGA <= 10. If one of the components was missing at an individual assessment point, Boolean-based remission for that assessment was set to missing.
Percentage of Participants in Clinical Disease Activity Index (CDAI) Remission [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up) ]
CDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician. CDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: CDAI =TJC28 + SJC28 + GH + GP Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity and GP=physician assessment of disease activity using a 10 cm visual analogue scale with 0 = best, 100 = worst). It ranges between 0 and 76. High score indicates worse outcome, low score indicates better outcome. Remission was achieved for a non-missing CDAI value <=2.8.
Change From Baseline in SDAI at All Assessment Time Points [ Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24 ]
SDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician and acute phase reactants. The SDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal-phalangeal I-V, proximal interphalangeal I-V and knees. It is calculated using the following formula: SDAI = TJC28 + SJC28 + GH + GP + CRP Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment, GP= physician assessment of disease activity using a 10 centimetre [cm] visual analogue scale [VAS] with 0 = best, 10 = worst), and CRP= C reactive Protein (in mg/L). It ranges between 0.1 and 86. High score indicates worse outcome, low score indicates better outcome. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
Change From Baseline in CDAI at All Assessment Time Points [ Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24 ]
CDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician. CDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: CDAI =TJC28 + SJC28 + GH + GP Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity and GP=physician assessment of disease activity using a 10 cm visual analogue scale with 0 = best, 100 = worst). It ranges between 0 and 76. High score indicates worse outcome, low score indicates better outcome. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at All Assessment Time Points [ Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24 ]
HAQ-DI is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in eight functional areas;dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each functional area contains at least two questions. For each question, there is a four level response set that is scored from 0 (without any difficulty) to 3 (unable to do). If aids or devices or physical assistance are used for a specific functional area and the maximum response of this functional area is 0 or 1 the according value is increased to a score of 2. HAQ-DI is only calculated if there are at least 6 functional area scores available. The average of these non-missing functional area scores defines the continuous HAQ-DI score ranging from 0 to 3. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
Change From Baseline in Pain Score at All Assessment Time Points [ Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and Week 24 ]
Participants assessed the severity of their current arthritis pain using a 100 unit visual analog scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponds to the magnitude of their pain. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
Change From Baseline in Physical and Mental Component Scores (PCS, MCS) and in Domain Scores of Short Form 36 (SF-36) at All Assessment Time Points [ Time Frame: Baseline and Weeks 4, 12, 24 ]
SF-36 is a generic health survey containing 36 questions covering 8 domains of health. SF-36 yields an 8-scale profile of functional health and well-being scores as well as PCS and MCS health summary scores. The version 2, 1-week recall questionnaire was used. Recoding, calculations and standardization were done as per the User's manual of SF-36. Domain scores were only calculated if less than half of the item scores were missing. All raw domain scores were transformed on a 0-100 scale (transformed domain scores) and then standardized into norm-based scores using Z-score. Following the transformation of the 8 domain scores into z-scores, the MCS and PCS were aggregated (AGG) using weights as PCS/MCS = 50 + (AGG_PHYS *10/AGG_MENT *10). High score (worse outcome) and low score (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at All Assessment Time Points [ Time Frame: Baseline and Weeks 4, 12, 24 ]
The FACIT-fatigue questionnaire is a participant reported measure developed to assess fatigue consisting of 13 statements regarding feeling fatigue using a numeric rating scale ranging from 0 to 4. For only two of the items (i.e. Answer 5 [An5] and An7) a higher value represents a lower fatigue; 11 of the item scores (i.e. HI7, HI12, An1, An2, An3, An4, An8, An12, An14, An15, An16) have to be reversed by subtracting the captured value from 4 (0 is turned to a 4; 1 into 3; 3 into 1; 4 into 0). After performing the reversals the sum of the non-missing individual items were multiplied by 13 and divided by the number of the non-missing individual items. The final score ranges from 0 to 52 with higher values representing a lower fatigue (i.e. a better quality of life). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
Change From Baseline in Brief Fatigue Inventory (BFI) Question 3 at All Assessment Time Points [ Time Frame: Baseline and Weeks 4, 12, 24 ]
BFI is a self-reported instrument consisting of nine questions which correlate well with quality-of-life measures. For this study, Question 3 only was used which asked about fatigue severity at its worst in the last 24 hours. A discrete 11 unit numeric reporting scale was used where 0 =No fatigue, and 10=As bad as you can imagine. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: Up to 62 weeks ]
An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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, is associated with liver injury and impaired liver function or any other situations as per Medical or Scientific judgment. Overall AEs and SAEs for the entire study duration until follow-up have been presented.
Number of Participants With Serious Infections [ Time Frame: Up to 62 weeks ]
An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious infections were categorized as AE of special interest. The number of participants with overall serious infections have been presented.
Number of Participants With Opportunistic Infections [ Time Frame: Up to 62 weeks ]
An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Opportunistic infections were categorized as AE of special interest. The number of participants with overall opportunistic infections have been presented.
Number of Participants With Pulmonary Events [ Time Frame: Up to 62 weeks ]
Pulmonary assessments were performed to determine the number of participants with pulmonary events including persistent cough, persistent dyspnea, and persistent Diffusing capacity of the lung for carbon monoxide (DLCO). Persistent is defined as any event with duration >=15 days. Baseline was defined as the last available assessment prior to the start of study treatment. The number of participants experiencing pulmonary events have been reported.
Number of Participants With Worst-case Post-Baseline Results for Pulse Oximetry [ Time Frame: Up to 62 weeks ]
Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen binds to hemoglobin in red blood cells when moving through the lungs. A pulse oximeter uses two frequencies of light (red and infrared) to determine the percentage of hemoglobin in the blood that is saturated with oxygen, that is called as blood oxygen saturation. Baseline was defined as the last available assessment prior to the start of study treatment. The number of participants with blood oxygen level < 80%, 80% to <90% and >=90% have been reported.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age >=18 years at the time of signing informed consent.
Meets ACR/EULAR 2010 RA Classification Criteria, with disease duration of >=12 weeks.
Swollen joint count of >=4 (66-joint count) and tender joint count of >=4 (68-joint count).
DAS28(CRP) >=3.2.
CRP >=5.0 milligram per litre (mg/L) at screening.
Must have previously received MTX (15-25 mg weekly) 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, e.g. hepatic or hematologic toxicity, or per local requirement.
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) >=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 women.
History of other inflammatory rheumatological 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 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.

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02504671

Locations

Show 64 study locations

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Bulgaria
GSK Investigational Site
Plovdiv, Bulgaria, 4000
GSK Investigational Site
Plovdiv, Bulgaria, 4002
GSK Investigational Site
Sofia, Bulgaria, 1431
GSK Investigational Site
Sofia, Bulgaria, 1606
Canada, Ontario
GSK Investigational Site
Brampton, Ontario, Canada, L6T 0G1
Canada
GSK Investigational Site
Barrie, Canada, L4M 6L2
Czechia
GSK Investigational Site
Brno, Czechia, 602 00
GSK Investigational Site
Bruntal, Czechia, 792 01
GSK Investigational Site
Praha 5, Czechia, 150 06
GSK Investigational Site
Praha, Czechia, 130 00
GSK Investigational Site
Uherske Hradiste, Czechia, 686 01
Estonia
GSK Investigational Site
Tallinn, Estonia, 10117
GSK Investigational Site
Tallinn, Estonia, 13419
Germany
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50937
GSK Investigational Site
Bad Doberan, Germany, 18209
GSK Investigational Site
Berlin, Germany, 14059
GSK Investigational Site
Hamburg, Germany, D-20095
Hungary
GSK Investigational Site
Budapest, Hungary, 1036
GSK Investigational Site
Kistarcsa, Hungary, 2143
GSK Investigational Site
Veszprém, Hungary, 8200
Italy
GSK Investigational Site
Milano, Lombardia, Italy, 20132
GSK Investigational Site
Bologna, Italy, 40138
GSK Investigational Site
Napoli, Italy, 80131
Mexico
GSK Investigational Site
Guadalajara, Jalisco, Mexico, 44650
GSK Investigational Site
Cuernavaca, Morelos, Mexico, 62170
GSK Investigational Site
Cuernavaca, Morelos, Mexico, 62290
GSK Investigational Site
Merida, Yucatán, Mexico, 97000
GSK Investigational Site
San Luis Potosí, Mexico, 78213
Poland
GSK Investigational Site
Bialystok, Poland, 15-351
GSK Investigational Site
Bydgoszcz, Poland, 85-168
GSK Investigational Site
Bytom, Poland, 41-902
GSK Investigational Site
Grodzisk Mazowiecki, Poland, 05-825
GSK Investigational Site
Lodz, Poland, 91-347
GSK Investigational Site
Lublin, Poland, 20-582
GSK Investigational Site
Torun, Poland, 87-100
GSK Investigational Site
Warszawa, Poland, 01-518
GSK Investigational Site
Warszawa, Poland, 02-653
Russian Federation
GSK Investigational Site
Moscow, Russian Federation, 119049
GSK Investigational Site
Novosibirsk, Russian Federation, 630099
GSK Investigational Site
Omsk, Russian Federation, 644111
GSK Investigational Site
Ryazan, Russian Federation, 390026
GSK Investigational Site
Saint Petersburg, Russian Federation, 192177
GSK Investigational Site
Tver, Russian Federation, 170036
GSK Investigational Site
Vladimir, Russian Federation, 600023
GSK Investigational Site
Yaroslavl, Russian Federation, 150003
GSK Investigational Site
Yaroslavl, Russian Federation, 150023
South Africa
GSK Investigational Site
Pretoria, Gauteng, South Africa, 1
GSK Investigational Site
Panorama / Cape Town, South Africa, 7500
GSK Investigational Site
Stellenbosch, South Africa, 7600
Spain
GSK Investigational Site
Coruña, Spain, 15006
GSK Investigational Site
Madrid, Spain, 28041
Ukraine
GSK Investigational Site
Ivano-Frankivsk, Ukraine, 76008
GSK Investigational Site
Kharkiv, Ukraine, 61029
GSK Investigational Site
Kharkiv, Ukraine, 61039
GSK Investigational Site
Kryvyi Rih, Ukraine, 50056
GSK Investigational Site
Lviv, Ukraine, 79013
GSK Investigational Site
Odesa, Ukraine, 65026
GSK Investigational Site
Poltava, Ukraine, 36011
GSK Investigational Site
Sumy, Ukraine, 40022
GSK Investigational Site
Vinnytsia, Ukraine, 21018
GSK Investigational Site
Vinnytsya, Ukraine, 21029
GSK Investigational Site
Zhytomyr, Ukraine, 10002
United Kingdom
GSK Investigational Site
Birmingham, United Kingdom, B15 2TH
GSK Investigational Site
Leeds, United Kingdom, LS7 4SA

Sponsors and Collaborators

GlaxoSmithKline

Investigators

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Study Director:	GSK Clinical Trials	GlaxoSmithKline

Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:

Study Protocol [PDF] March 11, 2016

Statistical Analysis Plan [PDF] August 26, 2015

More Information

Publications:

C Buckley, J Simon Campos, V Zhdan, K Davy, D Inman, E Fisheleva, A Gupta, M Layton, N Mitchell, J Patel, R Williamson, D Saurigny, P-P Tak, C Hawkes, B Becker. A Phase IIb Dose-Ranging Randomised Study of Efficacy, Patient-Reported Outcomes and Safety of the Anti-Granulocyte Macrophage Colony-Stimulating Factor Antibody Otilimab (GSK3196165) in Patients with Rheumatoid Arthritis. Lancet Rheumatol. 2020; DOI: 10.1016/S2665-9913(20)30229-0

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Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT02504671
Other Study ID Numbers:	201755 2014-003453-34 ( EudraCT Number )
First Posted:	July 22, 2015 Key Record Dates
Results First Posted:	April 4, 2019
Last Update Posted:	January 11, 2021
Last Verified:	December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	IPD for this study is available via the Clinical Study Data Request site.
Supporting Materials:	Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR)
Time Frame:	IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
Access Criteria:	Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL:	https://www.clinicalstudydatarequest.com/Posting.aspx?ID=20744

Keywords provided by GlaxoSmithKline:


DMARD-IR GSK3196165 Rheumatoid Arthritis

Additional relevant MeSH terms:

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Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases	Immune System Diseases Folic Acid Hematinics Vitamin B Complex Vitamins Micronutrients Physiological Effects of Drugs

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