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Trial record 2 of 9 for:    GSK3196165

Efficacy and Safety of GSK3196165 (Otilimab) Versus Placebo and Sarilumab in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biological Disease-modifying Antirheumatic Drug (DMARDs) and/or Janus Kinase (JAK) Inhibitors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04134728
Recruitment Status : Recruiting
First Posted : October 22, 2019
Last Update Posted : November 18, 2019
Sponsor:
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This is a Phase 3, randomized, multicenter, double-blind study to assess the safety and efficacy of GSK3196165 in combination with conventional synthetic disease modifying antirheumatic drugs (csDMARD[s]) or the treatment of adult participants with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD[s]) and/or Janus Kinase (JAK) inhibitors. The study will consist of a screening phase of up to 6 weeks followed by 24 week treatment phase in which participants will be randomized in ratio of 6:6:6:1:1:1 to GSK3196165 150 mg subcutaneously (SC) weekly,GSK3196165 90 mg SC weekly, sarilumab 200 mg SC every other week or placebo (three arms) respectively, all in combination with background csDMARD(s). At Week 12, participants in the three placebo arms will switch from placebo to active intervention (either GSK3196165 150 mg SC weekly, GSK3196165 90 mg SC weekly, or sarilumab 200 mg SC every other week). Following the treatment phase, there will be a safety follow-up visit at Week 34 for those participants who do not continue into the long term-extension study.

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Biological: GSK3196165 Biological: Sarilumab Drug: Placebo to GSK3196165/ Sarilumab Drug: csDMARDs Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 525 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomized to one of six intervention arms in ratio of 6:6:6:1:1:1
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Double blinded
Primary Purpose: Treatment
Official Title: A 24-week, Phase 3, Multicentre, Randomised, Double-blind, Efficacy and Safety Study, Comparing GSK3196165 With Placebo and With Sarilumab, in Combination With Conventional Synthetic DMARDs, in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biological DMARDs and/or Janus Kinase Inhibitors
Actual Study Start Date : October 31, 2019
Estimated Primary Completion Date : January 7, 2022
Estimated Study Completion Date : April 14, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Sarilumab

Arm Intervention/treatment
Experimental: GSK3196165 90 mg
Entire treatment period (24 Weeks): GSK3196165 90 mg subcutaneously (SC) injection once weekly. Participants will also receive a stable dose of csDMARD(s) as standard of care (SoC).
Biological: GSK3196165
GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered subcutaneously (SC).

Drug: csDMARDs
Stable dose of csDMARD(s) as standard of care (SoC).

Experimental: GSK3196165 150 mg
Entire treatment period (24 Weeks): GSK3196165 150 mg subcutaneously (SC) injection once weekly. Participants will also receive a stable dose of csDMARD(s) as standard of care (SoC).
Biological: GSK3196165
GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered subcutaneously (SC).

Drug: csDMARDs
Stable dose of csDMARD(s) as standard of care (SoC).

Active Comparator: Sarilumab 200 mg
Entire treatment period (24 Weeks): Sarilumab 200 mg subcutaneously (SC) injection every other week + placebo subcutaneously (SC) injection in the intervening weeks. Participants will also receive a stable dose of csDMARD(s) as standard of care (SoC).
Biological: Sarilumab
Sarilumab solution in pre-filled syringe (PFS) to be administered subcutaneously (SC).

Drug: Placebo to GSK3196165/ Sarilumab
Placebo sterile 0.9% w/v sodium chloride solution in vial/pre-filled syringe (PFS) to be administered subcutaneously (SC).

Drug: csDMARDs
Stable dose of csDMARD(s) as standard of care (SoC).

Placebo Comparator: Placebo sequence 1
From Week 0-11: Placebo subcutaneously (SC) injection once weekly. From Week 12 onwards: GSK3196165 90 mg subcutaneously (SC) injection once weekly. Participants will also receive a stable dose of csDMARD(s) as standard of care (SoC).
Biological: GSK3196165
GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered subcutaneously (SC).

Drug: Placebo to GSK3196165/ Sarilumab
Placebo sterile 0.9% w/v sodium chloride solution in vial/pre-filled syringe (PFS) to be administered subcutaneously (SC).

Drug: csDMARDs
Stable dose of csDMARD(s) as standard of care (SoC).

Placebo Comparator: Placebo sequence 2
From Week 0-11: Placebo subcutaneously (SC) injection once weekly. From Week 12 onwards: GSK3196165 150 mg subcutaneously (SC) injection once weekly. Participants will also receive a stable dose of csDMARD(s) as standard of care (SoC).
Biological: GSK3196165
GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered subcutaneously (SC).

Drug: Placebo to GSK3196165/ Sarilumab
Placebo sterile 0.9% w/v sodium chloride solution in vial/pre-filled syringe (PFS) to be administered subcutaneously (SC).

Drug: csDMARDs
Stable dose of csDMARD(s) as standard of care (SoC).

Placebo Comparator: Placebo sequence 3
From Week 0-11: Placebo subcutaneously (SC) injection once weekly. From Week 12 onwards: Sarilumab 200 mg subcutaneously (SC) injection every other week + placebo subcutaneously (SC) injection in the intervening weeks. Participants will also receive a stable dose of csDMARD(s) as standard of care (SoC).
Biological: Sarilumab
Sarilumab solution in pre-filled syringe (PFS) to be administered subcutaneously (SC).

Drug: Placebo to GSK3196165/ Sarilumab
Placebo sterile 0.9% w/v sodium chloride solution in vial/pre-filled syringe (PFS) to be administered subcutaneously (SC).

Drug: csDMARDs
Stable dose of csDMARD(s) as standard of care (SoC).




Primary Outcome Measures :
  1. Proportion of participants achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 superiority comparison with placebo [ Time Frame: Week 12 ]
    ACR20 is calculated as a 20% improvement from Baseline in both tender and swollen joint counts and a 20% improvement in 3 of the following 5 measures: patient global assessment of disease activity, physician global assessment of disease activity, pain visual analogue scale (VAS), health assessment questionnaire - disability index (HAQ-DI) and an acute-phase reactant (high sensitivity C-reactive protein [hsCRP] or erythrocyte sedimentation rate [ESR]). For comparison of GSK3196165 with placebo, the placebo sequences are combined into a single reporting group for Week 12 analysis.


Secondary Outcome Measures :
  1. Change from Baseline in health assessment questionnaire - disability index (HAQ-DI) at Week 12 [ Time Frame: Baseline and Week 12 ]
    HAQ-DI: 20-questions which assesses the degree of difficulty a participant has in accomplishing tasks in eight functional areas: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.

  2. Proportion of participants achieving Clinical disease activity index (CDAI) total score <=10 (CDAI Low disease activity [LDA]) at Week 12 [ Time Frame: Week 12 ]
    CDAI: Clinical Disease Activity Index for rheumatoid arthritis determines a composite score to determine disease severity using only clinical data. It is calculated by the simple sum of the 4 following parameters: Tender joint count (28), Swollen joint count (28), Patient's global assessment of arthritis and Physician's global assessment of arthritis both transformed to a 0-10 scale. Total score approximate range 0-76, higher score indicating more severe disease. Proportion of participants achieving CDAI total score <=10 at Week 12 will be summarized.

  3. Proportion of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 [ Time Frame: Week 24 ]
    CDAI: a composite score to determine disease severity using only clinical data: Tender joint count (28), Swollen joint count (28), Patient's global assessment of arthritis and Physician's global assessment of arthritis. Proportion of participants achieving CDAI total score <=10 at Week 24 will be summarized.

  4. Change from Baseline in CDAI total score at Week 12 [ Time Frame: Baseline and Week 12 ]
    CDAI: a composite score to determine disease severity using only clinical data. It is calculated by the simple sum of the 4 following parameters: Tender joint count (28), Swollen joint count (28), Patient's global assessment of arthritis and Physician's global assessment of arthritis both transformed to a 0-10 scale. Total score approximate range 0-76, higher score indicating more severe disease.

  5. Change from Baseline in CDAI total score at Week 24 [ Time Frame: Baseline and Week 24 ]
    CDAI: a composite score to determine disease severity using only clinical data. It is calculated by the simple sum of the 4 following parameters: Tender joint count (28), Swollen joint count (28), Patient's global assessment of arthritis and Physician's global assessment of arthritis both transformed to a 0-10 scale. Total score approximate range 0-76, higher score indicating more severe disease.

  6. Change from Baseline in Arthritis pain visual analogue scale (VAS) at Week 12 [ Time Frame: Baseline and Week 12 ]
    Patient's assessment of the severity of their arthritis pain over the past week, using a 100 unit VAS, with anchors "0" (no pain) and "100" (most severe pain).

  7. Change from Baseline in Arthritis pain VAS at Week 24 [ Time Frame: Baseline and Week 24 ]
    Patient's assessment of the severity of their arthritis pain over the past week, using a 100 unit VAS, with anchors "0" (no pain) and "100" (most severe pain).

  8. Proportion of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 12 [ Time Frame: Week 12 ]
    CDAI: a composite score to determine disease severity using only clinical data: Tender joint count (28), Swollen joint count (28), Patient's global assessment of arthritis and Physician's global assessment of arthritis. Proportion of participants achieving CDAI total score <=2.8 at Week 12 will be summarized.

  9. Proportion of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 [ Time Frame: Week 24 ]
    CDAI: a composite score to determine disease severity using only clinical data: Tender joint count (28), Swollen joint count (28), Patient's global assessment of arthritis and Physician's global assessment of arthritis. Proportion of participants achieving CDAI total score <=2.8 at Week 24 will be summarized.

  10. Proportion of participants achieving ACR20 at Week 24 [ Time Frame: Week 24 ]
    ACR20 is calculated as a 20% improvement from Baseline in both tender and swollen joint counts and a 20% improvement in 3 of the following 5 measures: patient global assessment of disease activity, physician global assessment of disease activity, pain VAS, HAQ-DI and an acute-phase reactant (hsCRP or ESR). Proportion of participants achieving ACR20 at Week 24 will be summarized.

  11. Proportion of participants achieving ACR50 at Week 12 [ Time Frame: Week 12 ]
    ACR50 is calculated as a 50% improvement from Baseline in both tender and swollen joint counts and a 50% improvement in 3 of the following 5 measures: patient global assessment of disease activity, physician global assessment of disease activity, pain VAS, HAQ-DI and an acute-phase reactant (hsCRP or ESR). Proportion of participants achieving ACR50 at Week 12 will be summarized.

  12. Proportion of participants achieving ACR50 at Week 24 [ Time Frame: Week 24 ]
    ACR50 is calculated as a 50% improvement from Baseline in both tender and swollen joint counts and a 50% improvement in 3 of the following 5 measures: Patient global assessment of disease activity, physician global assessment of disease activity, pain VAS, HAQ-DI and an acute-phase reactant (hsCRP or ESR). Proportion of participants achieving ACR50 at Week 24 will be summarized.

  13. Proportion of participants achieving ACR70 at Week 12 [ Time Frame: Week 12 ]
    ACR70 is calculated as a 70% improvement from Baseline in both tender and swollen joint counts and a 70% improvement in 3 of the following 5 measures: patient global assessment of disease activity, physician global assessment of disease activity, pain VAS, HAQ-DI and an acute-phase reactant (hsCRP or ESR). Proportion of participants achieving ACR70 at Week 12 will be summarized.

  14. Proportion of participants achieving ACR70 at Week 24 [ Time Frame: Week 24 ]
    ACR70 is calculated as a 70% improvement from Baseline in both tender and swollen joint counts and a 70% improvement in 3 of the following 5 measures: patient global assessment of disease activity, physician global assessment of disease activity, pain VAS, HAQ-DI and an acute-phase reactant (hsCRP or ESR). Proportion of participants achieving ACR70 at Week 24 will be summarized.

  15. Proportion of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12 [ Time Frame: Week 12 ]
    DAS28-CRP is a measure of RA disease activity calculated using the number of tender joints and swollen joints (28 joint count), hsCRP (milligrams per liter [mg/L]) and patient's global assessment of disease activity (transformed to a 0-10 scale). Total score approximate range 0-9.4, higher score indicating more severe disease. Proportion of participants achieving DAS28-CRP <=3.2 at Week 12 will be summarized.

  16. Proportion of participants with (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 24 [ Time Frame: Week 24 ]
    DAS28-CRP is a measure of RA disease activity calculated using the number of tender joints and swollen joints (28 joint count), hsCRP (mg/L) and patient's global assessment of disease activity (transformed to a 0-10 scale). Total score approximate range 0-9.4, higher score indicating more severe disease. Proportion of participants achieving DAS28-CRP <=3.2 at Week 24 will be summarized.

  17. Proportion of participants achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 [ Time Frame: Week 12 ]
    DAS28-ESR is a measure of RA disease activity calculated using the number of tender joints and swollen joints (28 joint count), ESR (millimeter [mm]/hour) and patient's global assessment of disease activity (transformed to a 0-10 scale). Total score approximate range 0-9.4, higher score indicating more severe disease. Proportion of participants achieving DAS28-ESR <=3.2 at Week 12 will be summarized.

  18. Proportion of participants with DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 [ Time Frame: Week 24 ]
    DAS28-ESR is a measure of RA disease activity calculated using the number of tender joints and swollen joints (28 joint count), ESR (millimeter [mm]/hour) and patient's global assessment of disease activity (transformed to a 0-10 scale). Total score approximate range 0-9.4, higher score indicating more severe disease. Proportion of participants achieving DAS28-ESR <2.6 at Week 24 will be summarized.

  19. Proportion of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 [ Time Frame: Week 12 ]
    DAS28-CRP is a measure of RA disease activity calculated using the number of tender joints and swollen joints (28 joint count), hsCRP (mg/L) and patient's global assessment of disease activity (transformed to a 0-10 scale). Total score approximate range 0-9.4, higher score indicating more severe disease. Proportion of participants achieving DAS28-CRP <2.6 at Week 12 will be summarized.

  20. Proportion of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 [ Time Frame: Week 24 ]
    DAS28-CRP is a measure of RA disease activity calculated using the number of tender joints and swollen joints (28 joint count), hsCRP (mg/L) and patient's global assessment of disease activity (transformed to a 0-10 scale). Total score approximate range 0-9.4, higher score indicating more severe disease. Proportion of participants achieving DAS28-CRP <2.6 at Week 24 will be summarized.

  21. Proportion of participants with DAS28-ESR <2.6 (DAS28-ESR Remission) at Week 12 [ Time Frame: Week 12 ]
    DAS28-ESR is a measure of RA disease activity calculated using the number of tender joints and swollen joints (28 joint count), ESR (mm/hour) and patient's global assessment of disease activity (transformed to a 0-10 scale). Total score approximate range 0-9.4, higher score indicating more severe disease. Proportion of participants achieving DAS28-ESR <2.6 at Week 12 will be summarized.

  22. Proportion of participants with DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 [ Time Frame: Week 24 ]
    DAS28-ESR is a measure of RA disease activity calculated using the number of tender joints and swollen joints (28 joint count), ESR (mm/hour) and patient's global assessment of disease activity (transformed to a 0-10 scale). Total score approximate range 0-9.4, higher score indicating more severe disease. Proportion of participants achieving DAS28-ESR <2.6 at Week 24 will be summarized.

  23. Proportion of participants with a good/moderate European League against Rheumatism (EULAR) response at Week 12 [ Time Frame: Week 12 ]
    Proportion of participants achieving a good/moderate EULAR response at Week 12 will be summarized.

  24. Proportion of participants achieving a good/moderate EULAR response at Week 24 [ Time Frame: Week 24 ]
    Proportion of participants achieving a good/moderate EULAR response at Week 24 will be summarized.

  25. Proportion of participants achieving ACR/EULAR remission at Week 12 [ Time Frame: Week 12 ]
    Proportion of participants achieving ACR/EULAR remission at Week 12 will be summarized.

  26. Proportion of participants achieving ACR/EULAR remission at Week 24 [ Time Frame: Week 24 ]
    Proportion of participants achieving ACR/EULAR remission at Week 24 will be summarized.

  27. Change from Baseline in DAS28(CRP) and DAS28-ESR at Week 12 [ Time Frame: Baseline and Week 12 ]
    DAS28 (CRP) and DAS28-ESR are measure of RA disease activity calculated using tender joint count and swollen joint count (28-joint count), hsCRP (mg/L)/ESR (mm/hour) and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, higher score indicating more disease activity.

  28. Change from Baseline in DAS28 (CRP) and DAS28-ESR at Week 24 [ Time Frame: Baseline and Week 24 ]
    DAS28 (CRP) and DAS28-ESR are measure of RA disease activity calculated using tender joint count and swollen joint count (28-joint count), hsCRP (mg/L)/ESR (mm/hour) and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, higher score indicating more disease activity.

  29. Change from Baseline in HAQ-DI at Week 24 [ Time Frame: Baseline and Week 24 ]
    HAQ-DI: 20-questions which assesses the degree of difficulty a participant has in accomplishing tasks in eight functional areas: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.

  30. Change from Baseline in Functional assessment of chronic illness therapy (FACIT)-Fatigue at Week 12 [ Time Frame: Baseline and Week 12 ]
    FACIT-fatigue is a validated patient-reported measure developed originally to assess fatigue in individuals with cancer and has subsequently been used and validated in numerous chronic conditions, including RA.

  31. Change from Baseline in FACIT-Fatigue at Week 24 [ Time Frame: Baseline and Week 24 ]
    FACIT-fatigue is a validated patient-reported measure developed originally to assess fatigue in individuals with cancer and has subsequently been used and validated in numerous chronic conditions, including RA.

  32. Change from Baseline in Short form (36) (SF-36) physical component scores at Week 12 [ Time Frame: Baseline and Week 12 ]
    SF-36 is a generic health survey that contains 36 questions covering eight domains of health: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue and general health perceptions. SF-36 scores each item on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.

  33. Change from Baseline in SF-36 physical component scores at Week 24 [ Time Frame: Baseline and Week 24 ]
    SF-36 is a generic health survey that contains 36 questions covering eight domains of health: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue and general health perceptions. SF-36 scores each item on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.

  34. Change from Baseline in SF-36 mental component scores at Week 12 [ Time Frame: Baseline and Week 12 ]
    SF-36 is a generic health survey that contains 36 questions covering eight domains of health: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue and general health perceptions. SF-36 scores each item on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.

  35. Change from Baseline in SF-36 mental component scores at Week 24 [ Time Frame: Baseline and Week 24 ]
    SF-36 is a generic health survey that contains 36 questions covering eight domains of health: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue and general health perceptions. SF-36 scores each item on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.

  36. Change from Baseline in SF-36 domain scores at Week 12 [ Time Frame: Baseline and Week 12 ]
    SF-36 is a generic health survey that contains 36 questions covering eight domains of health: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue and general health perceptions. SF-36 scores each item on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.

  37. Change from Baseline in SF-36 domain scores at Week 24 [ Time Frame: Baseline and Week 24 ]
    SF-36 is a generic health survey that contains 36 questions covering eight domains of health: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue and general health perceptions. SF-36 scores each item on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.

  38. Incidence of Adverse events (AEs), Serious adverse events (SAEs), Adverse event of special interest (AESIs) [ Time Frame: Up to Week 34 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. Protocol defined AESIs will be included.

  39. Change from Baseline in neutrophil, lymphocyte, platelet count (Giga cells per liter) at Week 12 [ Time Frame: Baseline and Week 12 ]
    Blood samples will be collected for the assessment of hematology parameters.

  40. Change from Baseline in neutrophil, lymphocyte, platelet count (Giga cells per liter) at Week 24 [ Time Frame: Baseline and Week 24 ]
    Blood samples will be collected for the assessment of hematology parameters.

  41. Change from Baseline in white blood cell (WBC) count (Giga cells per liter) at Week 12 [ Time Frame: Baseline and Week 12 ]
    Blood samples will be collected for the assessment of hematology parameters.

  42. Change from Baseline in white blood cell (WBC) count (Giga cells per liter) at Week 24 [ Time Frame: Baseline and Week 24 ]
    Blood samples will be collected for the assessment of hematology parameters.

  43. Change from Baseline in hemoglobin level (Grams per liter) Week 12 [ Time Frame: Baseline and Week 12 ]
    Blood samples will be collected for the assessment of hematology parameters.

  44. Change from Baseline in hemoglobin level (Grams per liter) Week 24 [ Time Frame: Baseline and Week 24 ]
    Blood samples will be collected for the assessment of hematology parameters.

  45. Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) gamma-glutamyl transferase(GGT) levels (International units per liter) at Week 12 [ Time Frame: Baseline and Week 12 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  46. Change from Baseline in AST, ALT, AP, GGT levels (International units per liter) at Week 24 [ Time Frame: Baseline and Week 24 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  47. Change from Baseline in albumin level (Grams per liter) at Week 12 [ Time Frame: Baseline and Week 12 ]
    Blood samples will be collected for the assessment of clinical chemistry parameter.

  48. Change from Baseline in albumin level (Grams per liter) at Week 24 [ Time Frame: Baseline and Week 24 ]
    Blood samples will be collected for the assessment of clinical chemistry parameter.

  49. Change from Baseline in total bilirubin (Micromoles per liter) at Week 12 [ Time Frame: Baseline and Week 12 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  50. Change from Baseline in total bilirubin (Micromoles per liter) at Week 24 [ Time Frame: Baseline and Week 24 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  51. Change from Baseline in total cholesterol (Millimoles per liter) at Week 12 [ Time Frame: Baseline and Week 12 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  52. Change from Baseline in total cholesterol (Millimoles per liter) at Week 24 [ Time Frame: Baseline and Week 24 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  53. Change from Baseline in fasting lipid profile: low-density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol (Millimoles per liter) at Week 12 [ Time Frame: Baseline and Week 12 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  54. Change from Baseline in fasting lipid profile: LDL cholesterol, HDL cholesterol (Millimoles per liter) at Week 24 [ Time Frame: Baseline and Week 24 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  55. Change from Baseline in fasting lipid profile triglycerides (Millimoles per liter) at Week 12 [ Time Frame: Baseline and Week 12 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  56. Change from Baseline in fasting lipid profile triglycerides (Millimoles per liter) at Week 24 [ Time Frame: Baseline and Week 24 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  57. Change from Baseline 4-beta-hydroxyl cholesterol, cholesterol at (Millimoles per liter) Week 12 [ Time Frame: Baseline and Week 12 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  58. Change from Baseline 4-beta-hydroxyl cholesterol, cholesterol at (Millimoles per liter) Week 24 [ Time Frame: Baseline and Week 24 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  59. Proportion of participants with National Cancer Institute (NCI) CTCAE >=Grade 3 hematological/clinical chemistry abnormalities [ Time Frame: Up to Week 34 ]
    Proportion of participants with NCI-CTCAE >=Grade 3 hematological/clinical chemistry abnormalities will be summarized.

  60. Concentrations of Granulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody [ Time Frame: Up to Week 34 ]
    Concentrations of GM-CSF autoantibodies will be determined.

  61. Number of participants with anti-GSK3196165 antibodies [ Time Frame: Up to Week 34 ]
    Presence of anti-GSK3196165 antibodies will be determined.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Key inclusion criteria:

  • ≥18 years of age
  • Has had RA for ≥6 months and was not diagnosed before 16 years of age
  • Has active disease, as defined by having both:*

    • ≥6/68 tender/painful joints (tender joint count [TJC]), and
    • ≥6/66 swollen joints (swollen joint count [SJC])
  • Has had an inadequate response despite currently taking at least one and at the most two concomitant csDMARDs for at least 12 weeks, from the following:

    • Methotrexate (MTX)
    • Hydroxychloroquine or chloroquine
    • Sulfasalazine
    • Leflunomide
    • Bucillamine
    • Iguratimod
    • Tacrolimus
  • Has had inadequate response to at least one bDMARD at an approved dose and/or at least one JAK inhibitors at an approved dose. In both cases this may be with or without combination with a csDMARD.

    • If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC or SJC.

Key exclusion criteria:

  • Has had any active and/or recurrent infections (excluding recurrent fungal infections of the nail bed) or has required management of acute or chronic infections.
  • Has received prior treatment with an antagonist of GM-CSF or its receptor.
  • Has known infection with human immunodeficiency virus (HIV) or current acute or chronic hepatitis B and/or hepatitis C.

Information from the National Library of Medicine

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): NCT04134728


Contacts
Layout table for location contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
Layout table for location information
United States, Florida
GSK Investigational Site Recruiting
DeBary, Florida, United States, 32713
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Kwabena Ayesu         
GSK Investigational Site Recruiting
Miami Lakes, Florida, United States, 33014
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Benidecto Fernandez         
GSK Investigational Site Recruiting
South Miami, Florida, United States, 33143
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Azarel Abinader         
United States, Illinois
GSK Investigational Site Recruiting
Chicago, Illinois, United States, 60607
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Dennis Levinson         
United States, Ohio
GSK Investigational Site Recruiting
Dayton, Ohio, United States, 45417
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Sanford M Wolfe         
United States, South Carolina
GSK Investigational Site Recruiting
Greenville, South Carolina, United States, 29601
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Josette Johnson         
United States, Texas
GSK Investigational Site Recruiting
Baytown, Texas, United States, 77521
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Sabeen Najam         
GSK Investigational Site Recruiting
San Marcos, Texas, United States, 78666
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Alissa Hassan         
GSK Investigational Site Recruiting
Tomball, Texas, United States, 77375
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Shaikh Arif Ali         
Sponsors and Collaborators
GlaxoSmithKline
Iqvia Pty Ltd
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04134728    
Other Study ID Numbers: 202018
First Posted: October 22, 2019    Key Record Dates
Last Update Posted: November 18, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made 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 will be made available within 6 months of publishing the results of the primary endpoints of the study.
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: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
bDMARD, GM-CSF, GSK3196165, Rheumatoid Arthritis, sarilumab, Otilimab
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