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Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

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ClinicalTrials.gov Identifier: NCT03980483
Recruitment Status : Recruiting
First Posted : June 10, 2019
Last Update Posted : October 8, 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 methotrexate (MTX), for the treatment of adult participants with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to MTX. The study will consist of a screening phase of up to 6 weeks followed by a 52-week treatment phase in which participants will be randomized in a ratio of 6:6:3:1:1:1 to receive GSK3196165 150 milligrams (mg) subcutaneous (SC) weekly, GSK3196165 90 mg SC weekly, tofacitinib capsules (cap) 5 mg twice a day or placebo (three arms, each placebo arm will have 12 weeks placebo followed by 40 weeks active treatment) respectively, all in combination with MTX. Following the treatment phase, there will be an 8-week safety follow up period for those participants who do not continue into the long term-extension study.

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Biological: GSK3196165 Drug: Tofacitinib 5 mg Drug: Placebo to GSK3196165 Drug: Placebo to tofacitinib Drug: Methotrexate Drug: Folic (or folinic) acid Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomized to one of six intervention arms in ratio of 6:6:3:1:1:1.
Masking: Double (Participant, Investigator)
Masking Description: Double blinded
Primary Purpose: Treatment
Official Title: A 52-week, Phase 3, Multicentre, Randomised, Double Blind, Efficacy and Safety Study Comparing GSK3196165 With Placebo and With Tofacitinib, in Combination With Methotrexate in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
Actual Study Start Date : May 16, 2019
Estimated Primary Completion Date : July 3, 2021
Estimated Study Completion Date : May 20, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GSK3196165 90 mg
Entire treatment period (52 Weeks): GSK3196165 90 mg SC injection once weekly + placebo cap twice daily. Participants will also receive a stable oral dose of MTX and >=5 mg/week folic (or folinic) acid as standard of care (SoC).
Biological: GSK3196165
GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.

Drug: Placebo to tofacitinib
Placebo cap (containing lactose) to be administered orally.

Drug: Methotrexate
Stable oral dose of MTX as SoC.

Drug: Folic (or folinic) acid
Folic (or folinic) acid >=5 mg/week.

Experimental: GSK3196165 150 mg
Entire treatment period (52 Weeks): GSK3196165 150 mg SC injection once weekly + placebo cap twice daily. Participants will also receive a stable oral dose of MTX and >=5 mg/week folic (or folinic) acid as SoC.
Biological: GSK3196165
GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.

Drug: Placebo to tofacitinib
Placebo cap (containing lactose) to be administered orally.

Drug: Methotrexate
Stable oral dose of MTX as SoC.

Drug: Folic (or folinic) acid
Folic (or folinic) acid >=5 mg/week.

Active Comparator: Tofacitinib
Entire treatment period (52 Weeks): Tofacitinib 5 mg cap twice daily + placebo SC injection once weekly. Participants will also receive a stable oral dose of MTX and >=5 mg/week folic (or folinic) acid as SoC.
Drug: Tofacitinib 5 mg
Tofacitinib cap (over encapsulated 5mg tablet) to be administered orally.

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

Drug: Methotrexate
Stable oral dose of MTX as SoC.

Drug: Folic (or folinic) acid
Folic (or folinic) acid >=5 mg/week.

Placebo Comparator: Placebo sequence 1
From Week 0-11: Placebo SC injection once weekly + placebo cap twice daily. From Week 12 onwards: GSK3196165 90 mg SC injection once weekly + placebo cap twice daily. Participants will also receive a stable oral dose of MTX and >=5 mg/week folic (or folinic) acid as SoC throughout.
Biological: GSK3196165
GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.

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

Drug: Placebo to tofacitinib
Placebo cap (containing lactose) to be administered orally.

Drug: Methotrexate
Stable oral dose of MTX as SoC.

Drug: Folic (or folinic) acid
Folic (or folinic) acid >=5 mg/week.

Placebo Comparator: Placebo sequence 2
From Week 0-11: Placebo SC injection once weekly + placebo capsule twice daily. From Week 12 onwards: GSK3196165 150 mg SC injection once weekly + placebo cap twice daily. Participants will also receive a stable oral dose of MTX and >=5 mg/week folic (or folinic) acid as SoC throughout.
Biological: GSK3196165
GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.

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

Drug: Placebo to tofacitinib
Placebo cap (containing lactose) to be administered orally.

Drug: Methotrexate
Stable oral dose of MTX as SoC.

Drug: Folic (or folinic) acid
Folic (or folinic) acid >=5 mg/week.

Placebo Comparator: Placebo sequence 3
From Week 0-11: Placebo SC injection once weekly + placebo cap twice daily. From Week 12 onwards: Tofacitinib 5 mg cap twice daily + placebo SC injection once weekly. Participants will also receive a stable oral dose of MTX and >=5 mg/week folic (or folinic) acid as SoC throughout.
Drug: Tofacitinib 5 mg
Tofacitinib cap (over encapsulated 5mg tablet) to be administered orally.

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

Drug: Placebo to tofacitinib
Placebo cap (containing lactose) to be administered orally.

Drug: Methotrexate
Stable oral dose of MTX as SoC.

Drug: Folic (or folinic) acid
Folic (or folinic) acid >=5 mg/week.




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 VAS, 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. 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.

  2. Change from Baseline in health assessment questionnaire - disability index (HAQ-DI) at Week 12 [ Time Frame: 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.

  3. Proportion of participants achieving ACR20 at Week 12: non-inferiority comparison with tofacitinib [ 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 VAS, HAQ-DI and an acute-phase reactant (high sensitivity C-reactive protein [hsCRP] or erythrocyte sedimentation rate [ESR]). Proportion of participants achieving ACR20 at Week 12 will be summarized.

  4. 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.

  5. Proportion of participants achieving CDAI total score <=10 (CDAI LDA) at Week 52 [ Time Frame: Week 52 ]
    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 52 will be summarized.

  6. 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.

  7. 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.

  8. Proportion of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 52 [ Time Frame: Week 52 ]
    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 52 will be summarized.

  9. Proportion of participants achieving ACR20/50/70 at Week 12 [ Time Frame: Week 12 ]
    ACR20/50/70 is calculated as a 20%/50%/70% improvement from baseline in both tender and swollen joint counts and a 20%/50%/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 ACR20/50/70 at Week 12 will be summarized.

  10. Proportion of participants achieving ACR20/50/70 at Week 24 [ Time Frame: Week 24 ]
    ACR20/50/70 is calculated as a 20%/50%/70% improvement from baseline in both tender and swollen joint counts and a 20%/50%/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 ACR20/50/70 at Week 24 will be summarized.

  11. Proportion of participants achieving ACR20/50/70 at Week 52 [ Time Frame: Week 52 ]
    ACR20/50/70 is calculated as a 20%/50%/70% improvement from baseline in both tender and swollen joint counts and a 20%/50%/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 ACR20/50/70 at Week 52 will be summarized.

  12. 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 (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.

  13. 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 (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.

  14. Proportion of participants achieving 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.

  15. Proportion of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 [ Time Frame: Week 24 ]
    DAS28-ESR is a derived measurement with differential weighting given to each component: tender joint count and swollen joint count (28-joint count), 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. Proportion of participants achieving DAS28 ESR <=3.2 at Week 24 will be summarized.

  16. Proportion of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 52 [ Time Frame: Week 52 ]
    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 52 will be summarized.

  17. Proportion of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 52 [ Time Frame: Week 52 ]
    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 <=3.2 at Week 52 will be summarized.

  18. 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.

  19. Proportion of participants achieving 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.

  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 achieving DAS28 ESR <2.6 (DAS28-ESR Remission) 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 (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.

  22. Proportion of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 52 [ Time Frame: Week 52 ]
    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 52 will be summarized.

  23. Proportion of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 52 [ Time Frame: Week 52 ]
    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 52 will be summarized.

  24. Proportion of participants achieving a good/moderate EULAR response at Week 12 [ Time Frame: Week 12 ]
    Proportion of participants achieving a good/moderate EULAR response at Week 12 will be summarized.

  25. 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.

  26. Proportion of participants achieving a good/moderate EULAR response at Week 52 [ Time Frame: Week 52 ]
    Proportion of participants achieving a good/moderate EULAR response at Week 52 will be summarized.

  27. 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.

  28. 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.

  29. Proportion of participants achieving ACR/EULAR remission at Week 52 [ Time Frame: Week 52 ]
    Proportion of participants achieving ACR/EULAR remission at Week 52 will be summarized.

  30. Proportion of participants achieving no radiographic progression at Week 12 [ Time Frame: Week 12 ]
    Van der Heijde mTSS is a scoring method which utilized for scoring radiographs of hands and feet in rheumatoid arthritis. No radiographic progression defined as a change from baseline in van der Heijde modified total sharp score (mTSS) score of ≤0.5. Proportion of participants achieving no radiographic progression at Week 12 will be summarized.

  31. Proportion of participants achieving no radiographic progression at Week 24 [ Time Frame: Week 24 ]
    Van der Heijde mTSS is a scoring method which utilized for scoring radiographs of hands and feet in rheumatoid arthritis. No radiographic progression defined as a change from baseline in van der Heijde modified total sharp score (mTSS) score of ≤0.5. Proportion of participants achieving no radiographic progression at Week 24 will be summarized.

  32. Proportion of participants achieving no radiographic progression at Week 52 [ Time Frame: Week 52 ]
    Van der Heijde mTSS is a scoring method which utilized for scoring radiographs of hands and feet in rheumatoid arthritis. No radiographic progression defined as a change from baseline in van der Heijde modified total sharp score (mTSS) score of ≤0.5. Proportion of participants achieving no radiographic progression at Week 52 will be summarized.

  33. Change from Baseline in CDAI total score 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.

  34. Change from Baseline in CDAI total score 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.

  35. Change from Baseline in CDAI total score at Week 52 [ Time Frame: Week 52 ]
    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.

  36. Change from Baseline in DAS28-CRP/DAS28-ESR at Week 12 [ Time Frame: 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.

  37. Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 [ Time Frame: 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.

  38. Change from Baseline in DAS28-CRP/DAS28-ESR at Week 52 [ Time Frame: Week 52 ]
    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.

  39. Change from Baseline in Van der Heijde mTSS at Week 12 [ Time Frame: Week 12 ]
    Van der Heijde mTSS is a scoring method which utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes, in each hand, 16 areas of erosions, and 15 areas for joint space narrowing, and in each foot, 6 areas for erosions and 6 areas joint space narrowing.

  40. Change from Baseline in Van der Heijde mTSS at Week 24 [ Time Frame: Week 24 ]
    Van der Heijde mTSS is a scoring method which utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes, in each hand, 16 areas of erosions, and 15 areas for joint space narrowing, and in each foot, 6 areas for erosions and 6 areas joint space narrowing.

  41. Change from Baseline in Van der Heijde mTSS at Week 52 [ Time Frame: Week 52 ]
    Van der Heijde mTSS is a scoring method which utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes, in each hand, 16 areas of erosions, and 15 areas for joint space narrowing, and in each foot, 6 areas for erosions and 6 areas joint space narrowing.

  42. Change from Baseline in HAQ-DI at Week 24 [ Time Frame: 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.

  43. Change from Baseline in HAQ-DI at Week 52 [ Time Frame: Week 52 ]
    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.

  44. Change from Baseline in Arthritis pain Visual analogue scale (VAS) at Week 12 [ Time Frame: Week 12 ]
    Participants' 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).

  45. Change from Baseline in Arthritis pain VAS at Week 24 [ Time Frame: Week 24 ]
    Participants' 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).

  46. Change from Baseline in Arthritis pain VAS at Week 52 [ Time Frame: Week 52 ]
    Participants' 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).

  47. Change from Baseline in Short form (36) (SF-36) physical component scores at Week 12 [ Time Frame: 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.

  48. Change from Baseline in SF-36 mental component scores at Week 12 [ Time Frame: 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.

  49. Change from Baseline in SF-36 domain scores at Week 12 [ Time Frame: 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.

  50. Change from Baseline in SF-36 physical component scores at Week 24 [ Time Frame: 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.

  51. Change from Baseline in SF-36 mental component scores at Week 24 [ Time Frame: 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.

  52. Change from Baseline in SF-36 domain scores at Week 24 [ Time Frame: 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.

  53. Change from Baseline in SF-36 physical component scores at Week 52 [ Time Frame: Week 52 ]
    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.

  54. Change from Baseline in SF-36 mental component scores at Week 52 [ Time Frame: Week 52 ]
    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.

  55. Change from Baseline in SF-36 domain scores at Week 52 [ Time Frame: Week 52 ]
    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.

  56. Change from Baseline in Functional assessment of chronic illness therapy (FACIT)-Fatigue at Week 12 [ Time Frame: 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.

  57. Change from Baseline in FACIT-Fatigue at Week 24 [ Time Frame: 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.

  58. Change from Baseline in FACIT-Fatigue at Week 52 [ Time Frame: Week 52 ]
    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.

  59. Incidence of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) [ Time Frame: Up to Week 59 ]
    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.

  60. Change from Baseline in white blood cell count [ Time Frame: Baseline and up to Week 59 ]
    Blood samples will be collected for the assessment of white blood cell count.

  61. Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes [ Time Frame: Baseline and up to Week 59 ]
    Blood samples will be collected for the assessment of hematology parameters.

  62. Change from Baseline in hematology parameter of haemoglobin [ Time Frame: Baseline and up to Week 59 ]
    Blood samples will be collected for the assessment of hematology parameters.

  63. Change from Baseline in clinical chemistry parameter of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), γ-Glutamyl transpeptidase (GGT) [ Time Frame: Baseline and up to Week 59 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  64. Change from Baseline in clinical chemistry parameter of total bilirubin [ Time Frame: Baseline and up to Week 59 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  65. Change from Baseline in clinical chemistry parameter of albumin [ Time Frame: Baseline and up to Week 59 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  66. Change from Baseline in fasting lipid profile parameter of total cholesterol [ Time Frame: Baseline and up to Week 59 ]
    Blood samples will be collected for the assessment of fasting lipid profile parameters.

  67. Change from Baseline in fasting lipid profile parameter of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein-cholesterol [ Time Frame: Baseline and up to Week 59 ]
    Blood samples will be collected for the assessment of fasting lipid profile parameters.

  68. Change from Baseline in fasting lipid profile parameter of triglycerides [ Time Frame: Baseline and up to Week 59 ]
    Blood samples will be collected for the assessment of fasting lipid profile parameters.

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

  70. Concentrations of Granulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody [ Time Frame: Up to Week 59 ]
    Concentrations of GM-CSF autoantibodies will be determined.

  71. Number of participants with anti-GSK3196165 antibodies [ Time Frame: Up to Week 59 ]
    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.


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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

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 (TJC), and
    • ≥6/66 swollen joints (SJC)
  • Has at least 1 bone erosion present on hand/wrist or foot radiographs
  • Has had an inadequate response to MTX, despite currently taking MTX 15-25 mg/week** oral or injected

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

      • A lower dose of 7.5 mg/week is acceptable if reduced for reasons of intolerance to MTX or per local requirement.

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 or targeted synthetic DMARDs (either experimental or approved), including Janus kinase (JAK) inhibitors
  • Has received prior treatment with a biologic DMARD that was discontinued due to an inadequate response

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): NCT03980483


Contacts
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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

  Show 33 Study Locations
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: NCT03980483     History of Changes
Other Study ID Numbers: 201790
First Posted: June 10, 2019    Key Record Dates
Last Update Posted: October 8, 2019
Last Verified: October 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:
Rheumatoid arthritis
GSK3196165
Tofacitinib
Methotrexate
Placebo
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
Methotrexate
Tofacitinib
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Protein Kinase Inhibitors