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 (contRAst 3)

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

This study (contRAst 3 [202018: NCT04134728]) is a Phase 3, randomized, multicenter, double-blind study to assess the safety and efficacy of GSK3196165 in combination with conventional (cs) DMARD[s]) or the treatment of adult participants with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to biologic (b) DMARD[s]) and/or 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 milligrams (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). Participants who, in investigator's judgement will benefit from extended treatment with GSK3196165, may be included in the long-term extension study (contRAst X [209564: NCT04333147]). Any participant who does not transition into study 209564 will undergo a safety follow-up visit at Week 34 (corresponding to 12 weeks after the last potential dose of sarilumab, at Week 22).

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Biological: GSK3196165 (Otilimab); Drug: csDMARDs; Biological: Sarilumab; Drug: Placebo to GSK3196165/ Sarilumab

• Study Type: Interventional
• Enrollment (Actual): 550
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1430CKE
    • GSK Investigational Site
  • Ciudad Autónoma de Buenos Aires, Argentina, C1426BOR
    • GSK Investigational Site
  • San Juan, Argentina, 5400
    • GSK Investigational Site
  • Buenos Aires
    • Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina, C1430EGF
      • GSK Investigational Site
    • Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina, C1417
      • GSK Investigational Site
    • Ciudad Autonoma Buenos aires, Buenos Aires, Argentina, C1046AAQ
      • GSK Investigational Site
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, 1426
      • GSK Investigational Site
    • La Palta, Buenos Aires, Argentina, B1900AXI
      • GSK Investigational Site
    • Mar del Plata, Buenos Aires, Argentina, B7600FYK
      • GSK Investigational Site
    • San Isidro, Buenos Aires, Argentina, 1643
      • GSK Investigational Site
    • San Nicolas, Buenos Aires, Argentina, B2900DMH
      • GSK Investigational Site
• Belgium
  • Mons, Belgium, 7000
    • GSK Investigational Site
• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6L2
      • GSK Investigational Site
    • Brampton, Ontario, Canada, L6T 0G1
      • GSK Investigational Site
  • Quebec
    • Trois-Rivieres, Quebec, Canada, G8Z 1Y2
      • GSK Investigational Site
• Czechia
  • Brno, Czechia, 638 00
    • GSK Investigational Site
  • Brno, Czechia, 65691
    • GSK Investigational Site
  • Ostrava, Czechia, 70200
    • GSK Investigational Site
  • Praha 11, Czechia, 148 00
    • GSK Investigational Site
  • Praha 2, Czechia, 128 50
    • GSK Investigational Site
  • Praha 5, Czechia, 150 06
    • GSK Investigational Site
  • Uherske Hradiste, Czechia, 686 01
    • GSK Investigational Site
  • Zlin, Czechia, 760 01
    • GSK Investigational Site
• Germany
  • Hamburg, Germany, D-20095
    • GSK Investigational Site
  • Magdeburg, Germany, 39120
    • GSK Investigational Site
  • Schleswig-Holstein
    • Rendsburg, Schleswig-Holstein, Germany, 24768
      • GSK Investigational Site
• Hungary
  • Budapest, Hungary, 1023
    • GSK Investigational Site
  • Szekesfehervar, Hungary, 8000
    • GSK Investigational Site
  • Veszprem, Hungary, H-8200
    • GSK Investigational Site
• Italy
  • Veneto
    • Verona, Veneto, Italy, 37126
      • GSK Investigational Site
• Japan
  • Aichi, Japan, 455-8530
    • GSK Investigational Site
  • Aichi, Japan, 457-8511
    • GSK Investigational Site
  • Aichi, Japan, 460-0001
    • GSK Investigational Site
  • Chiba, Japan, 270-2296
    • GSK Investigational Site
  • Fukuoka, Japan, 807-8555
    • GSK Investigational Site
  • Hokkaido, Japan, 060-8648
    • GSK Investigational Site
  • Hokkaido, Japan, 063-0811
    • GSK Investigational Site
  • Hyogo, Japan, 673-1462
    • GSK Investigational Site
  • Hyogo, Japan, 675-1392
    • GSK Investigational Site
  • Ibaraki, Japan, 312-0057
    • GSK Investigational Site
  • Kagoshima, Japan, 891-0133
    • GSK Investigational Site
  • Kanagawa, Japan, 245-8575
    • GSK Investigational Site
  • Kochi, Japan, 781-0112
    • GSK Investigational Site
  • Kumamoto, Japan, 862-0976
    • GSK Investigational Site
  • Miyagi, Japan, 980-8574
    • GSK Investigational Site
  • Nagasaki, Japan, 857-1195
    • GSK Investigational Site
  • Saitama, Japan, 359-1111
    • GSK Investigational Site
  • Tokyo, Japan, 142-0054
    • GSK Investigational Site
  • Tokyo, Japan, 104-8560
    • GSK Investigational Site
• Korea, Republic of
  • Incheon, Korea, Republic of, 400-711
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 04763
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 03722
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 3080
    • GSK Investigational Site
• Lithuania
  • Klaipeda, Lithuania, LT-92288
    • GSK Investigational Site
  • Siauliai, Lithuania, 76231
    • GSK Investigational Site
• Poland
  • Bialystok, Poland, 15-879
    • GSK Investigational Site
  • Bydgoszcz, Poland, 85-168
    • GSK Investigational Site
  • Gdansk, Poland, 80-382
    • GSK Investigational Site
  • Gdynia, Poland, 81-537
    • GSK Investigational Site
  • Katowice, Poland, 40-040
    • GSK Investigational Site
  • Katowice, Poland, 40-282
    • GSK Investigational Site
  • Kraków, Poland, 30-363
    • GSK Investigational Site
  • Lodz, Poland, 90-127
    • GSK Investigational Site
  • Poznan, Poland, 60-702
    • GSK Investigational Site
  • Poznan, Poland, 60-773
    • GSK Investigational Site
  • Sochaczew, Poland, 96-500
    • GSK Investigational Site
  • Torun, Poland, 87-100
    • GSK Investigational Site
  • Warszawa, Poland, 01-192
    • GSK Investigational Site
  • Warszawa, Poland, 00-874
    • GSK Investigational Site
  • Warszawa, Poland, 00-465
    • GSK Investigational Site
  • Warszawa, Poland, 02-118
    • GSK Investigational Site
  • Wrocław, Poland, 50-381
    • GSK Investigational Site
• South Africa
  • Cape Town, South Africa, 7500
    • GSK Investigational Site
  • Kempton Park, South Africa, 1619
    • GSK Investigational Site
  • Pretoria, South Africa, 0002
    • GSK Investigational Site
  • Stellenbosch, South Africa, 7600
    • GSK Investigational Site
  • Gauteng
    • Pretoria, Gauteng, South Africa, 184
      • GSK Investigational Site
  • KwaZulu- Natal
    • Durban, KwaZulu- Natal, South Africa, 4319
      • GSK Investigational Site
• Spain
  • A Coruña, Spain, 15006
    • GSK Investigational Site
  • Elche, Spain, 03203
    • GSK Investigational Site
  • Santander, Spain, 39008
    • GSK Investigational Site
  • Santiago de Compostela, Spain, 15706
    • GSK Investigational Site
  • Valencia, Spain, 46010
    • GSK Investigational Site
• United Kingdom
  • Essex
    • Romford, Essex, United Kingdom, RM1 3PJ
      • GSK Investigational Site
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA6 2RN
      • GSK Investigational Site
• United States
  • Arizona
    • Mesa, Arizona, United States, 85210
      • GSK Investigational Site
    • Phoenix, Arizona, United States, 85032
      • GSK Investigational Site
    • Sun City, Arizona, United States, 85351
      • GSK Investigational Site
    • Tucson, Arizona, United States, 85704
      • GSK Investigational Site
  • California
    • Covina, California, United States, 91722
      • GSK Investigational Site
    • San Diego, California, United States, 92128
      • GSK Investigational Site
    • Tujunga, California, United States, 91042
      • GSK Investigational Site
    • Upland, California, United States, 91786
      • GSK Investigational Site
    • Whittier, California, United States, 90602
      • GSK Investigational Site
  • Florida
    • Brandon, Florida, United States, 33511
      • GSK Investigational Site
    • DeBary, Florida, United States, 32713
      • GSK Investigational Site
    • Jacksonville, Florida, United States, 32207
      • GSK Investigational Site
    • Miami, Florida, United States, 33173
      • GSK Investigational Site
    • Miami, Florida, United States, 33134
      • GSK Investigational Site
    • Miami, Florida, United States, 33165
      • GSK Investigational Site
    • Miami, Florida, United States, 33155
      • GSK Investigational Site
    • Miami Lakes, Florida, United States, 33014
      • GSK Investigational Site
    • Tampa, Florida, United States, 33613
      • GSK Investigational Site
    • Tampa, Florida, United States, 33614
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • GSK Investigational Site
    • Newnan, Georgia, United States, 30265
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • GSK Investigational Site
    • Skokie, Illinois, United States, 60076
      • GSK Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • GSK Investigational Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • GSK Investigational Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • GSK Investigational Site
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • GSK Investigational Site
    • Dayton, Ohio, United States, 45417
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • GSK Investigational Site
    • Oklahoma City, Oklahoma, United States, 73112
      • GSK Investigational Site
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • GSK Investigational Site
    • Baytown, Texas, United States, 77521
      • GSK Investigational Site
    • College Station, Texas, United States, 77845
      • GSK Investigational Site
    • Colleyville, Texas, United States, 76034
      • GSK Investigational Site
    • Houston, Texas, United States, 77090
      • GSK Investigational Site
    • Houston, Texas, United States, 77065
      • GSK Investigational Site
    • Houston, Texas, United States, 77089
      • GSK Investigational Site
    • Lubbock, Texas, United States, 79410
      • GSK Investigational Site
    • Plano, Texas, United States, 75024
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
    • San Marcos, Texas, United States, 78666
      • GSK Investigational Site
    • The Woodlands, Texas, United States, 77382
      • GSK Investigational Site
    • Tomball, Texas, United States, 77375
      • GSK Investigational Site
    • Waco, Texas, United States, 76710
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK3196165 90 mg; Entire treatment period (24 Weeks): GSK3196165 90 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as standard of care (SoC).	Biological: GSK3196165 (Otilimab); GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.; Drug: csDMARDs; Stable dose of csDMARD(s) as SoC.
Experimental: GSK3196165 150 mg; Entire treatment period (24 Weeks): GSK3196165 150 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.	Biological: GSK3196165 (Otilimab); GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.; Drug: csDMARDs; Stable dose of csDMARD(s) as SoC.
Active Comparator: Sarilumab 200 mg; Entire treatment period (24 Weeks): Sarilumab 200 mg SC injection every other week + placebo SC injection in the intervening weeks. Participants will also receive a stable dose of csDMARD(s) as SoC.	Drug: csDMARDs; Stable dose of csDMARD(s) as SoC.; Biological: Sarilumab; Sarilumab solution in PFS to be administered SC.; Drug: Placebo to GSK3196165/ Sarilumab; Placebo sterile 0.9 percentage (%) weight by volume (w/v) sodium chloride solution in vial/PFS to be administered SC.
Placebo Comparator: Placebo sequence 1; From Week 0-11: Placebo SC injection once weekly. From Week 12 onwards: GSK3196165 90 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.	Biological: GSK3196165 (Otilimab); GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.; Drug: csDMARDs; Stable dose of csDMARD(s) as SoC.; Drug: Placebo to GSK3196165/ Sarilumab; Placebo sterile 0.9 percentage (%) weight by volume (w/v) sodium chloride solution in vial/PFS to be administered SC.
Placebo Comparator: Placebo sequence 2; From Week 0-11: Placebo SC injection once weekly. From Week 12 onwards: GSK3196165 150 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.	Biological: GSK3196165 (Otilimab); GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.; Drug: csDMARDs; Stable dose of csDMARD(s) as SoC.; Drug: Placebo to GSK3196165/ Sarilumab; Placebo sterile 0.9 percentage (%) weight by volume (w/v) sodium chloride solution in vial/PFS to be administered SC.
Placebo Comparator: Placebo sequence 3; From Week 0-11: Placebo SC injection once weekly. From Week 12 onwards: Sarilumab 200 mg SC injection every other week + placebo SC injection in the intervening weeks. Participants will also receive a stable dose of csDMARD(s) as SoC.	Drug: csDMARDs; Stable dose of csDMARD(s) as SoC.; Biological: Sarilumab; Sarilumab solution in PFS to be administered SC.; Drug: Placebo to GSK3196165/ Sarilumab; Placebo sterile 0.9 percentage (%) weight by volume (w/v) sodium chloride solution in vial/PFS to be administered SC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With 20% Improvement in American College of Rheumatology Criteria (ACR20) at Week 12 Superiority Comparison With Placebo	ACR20 is calculated as a 20% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP)). For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) (Versus Placebo) at Week 12	Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the difficulty of a participant in eight domains of daily living activities: Dressing & grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, Common daily activities. Overall HAQ-DI score was computed as the sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Percentage of Participants With Clinical Disease Activity Index (CDAI) Total Score <=10 (CDAI Low Disease Activity [LDA]) at Week 12	Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Week 12
Percentage of Participants With CDAI Total Score <=10 (CDAI LDA) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. LDA is achieved when CDAI total score <=10.	Week 24
Percentage of Participants With CDAI Total Score <=10 (CDAI LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. LDA is achieved when CDAI total score <=10.	Week 24
Change From Baseline in CDAI Total Score at Week 12	Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. A negative CDAI total score change from baseline indicates an improvement in disease activity. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in CDAI Total Score at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity.	Baseline (Day 01) and Week 24
Change From Baseline in CDAI Total Score at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity.	Baseline (Day 01) and Week 24
Change From Baseline in Arthritis Pain Visual Analogue Scale (VAS) at Week 12	For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in Arthritis Pain VAS at Week 24 for Treatment Arms That Started Study Intervention From Day 1	For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement.	Baseline (Day 01) and Week 24
Change From Baseline in Arthritis Pain VAS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement.	Baseline (Day 01) and Week 24
Percentage of Participants With CDAI Total Score <=2.8 (CDAI Remission) at Week 12	Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Week 12
Percentage of Participants With CDAI Total Score <=2.8 (CDAI Remission) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity.	Week 24
Percentage of Participants With CDAI Total Score <=2.8 (CDAI Remission) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity.	Week 24
Percentage of Participants With ACR20 at Week 24 for Treatment Arms That Started Study Intervention From Day 1	ACR20 is calculated as a 20% improvement from Baseline in TJC68 and SJC66 and a 20% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).	Week 24
Percentage of Participants With ACR20 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	ACR20 is calculated as a 20% improvement from Baseline in TJC68 and SJC66 and a 20% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).	Week 24
Percentage of Participants With 50% Improvement in American College of Rheumatology Criteria (ACR50) at Week 12	ACR50 is calculated as a 50% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 50% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP)). For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Week 12
Percentage of Participants With ACR50 at Week 24 for Treatment Arms That Started Study Intervention From Day 1	ACR50 is calculated as a 50% improvement from Baseline in TJC68 and SJC66 and a 50% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).	Week 24
Percentage of Participants With ACR50 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	ACR50 is calculated as a 50% improvement from Baseline in TJC68 and SJC66 and a 50% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).	Week 24
Percentage of Participants With 70% Improvement in American College of Rheumatology Criteria (ACR70) at Week 12	ACR70 is calculated as a 70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP)). For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Week 12
Percentage of Participants With ACR70 at Week 24 for Treatment Arms That Started Study Intervention From Day 1	ACR70 is calculated as a 70% improvement from Baseline in TJC68 and SJC66 and a 70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).	Week 24
Percentage of Participants With ACR70 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	ACR70 is calculated as a 70% improvement from Baseline in TJC68 and SJC66 and a 70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).	Week 24
Percentage of Participants With Disease Activity Score Using 28 Joint Count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12	The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicates less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP<=3.2. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Week 12
Percentage of Participants With DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicates less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP<=3.2 . A negative change from baseline in DAS28-CRP indicates an improvement.	Week 24
Percentage of Participants With DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicates less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP<=3.2 . A negative change from baseline in DAS28-CRP indicates an improvement.	Week 24
Percentage of Participants With DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12	The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Week 12
Percentage of Participants With DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement.	Week 24
Percentage of Participants With DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement.	Week 24
Percentage of Participants With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12	The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicates less disease activity. Remission is achieved when DAS28-CRP <2.6. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Week 12
Percentage of Participants With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	The DAS28-CRP arthritis is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicates less disease activity. Remission is achieved when DAS28-CRP <2.6. A negative change from baseline in DAS28-CRP indicates an improvement.	Week 24
Percentage of Participants With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	The DAS28-CRP arthritis is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicates less disease activity. Remission is achieved when DAS28-CRP <2.6. A negative change from baseline in DAS28-CRP indicates an improvement.	Week 24
Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) at Week 12	The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicates less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Week 12
Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for Treatment Arms That Started Study Intervention From Day 1	The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicates less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement.	Week 24
Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicates less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement.	Week 24
Percentage of Participants With a Good/Moderate European League Against Rheumatism (EULAR) Response at Week 12	DAS28-CRP and DAS28-ESR scores categorized using EULAR response criteria. Response based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to baseline (Good response = DAS28 change >1.2 with current DAS28 ≤3.2; Moderate response = DAS28 change >0.6 with current DAS28 >3.2-5.1; Non-response = DAS28 change ≤0.6 and current DAS28 >5.1). For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Week 12
Percentage of Participants With a Good/Moderate EULAR Response at Week 24 for Treatment Arms That Started Study Intervention From Day 1	DAS28-CRP and DAS28-ESR scores categorised using EULAR response criteria. Response based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to baseline (Good response = DAS28 change >1.2 with current DAS28 ≤3.2; Moderate response = DAS28 change >0.6 with current DAS28 >3.2-5.1; Non-response = DAS28 change ≤0.6 and current DAS28 >5.1).	Week 24
Percentage of Participants With a Good/Moderate EULAR Response at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	DAS28-CRP and DAS28-ESR scores categorised using EULAR response criteria. Response based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to baseline (Good response = DAS28 change >1.2 with current DAS28 ≤3.2; Moderate response = DAS28 change >0.6 with current DAS28 >3.2-5.1; Non-response = DAS28 change ≤0.6 and current DAS28 >5.1).	Week 24
Percentage of Participants With ACR/EULAR Remission at Week 12	Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) ≤ 1, Swollen Joint Count 66 (SJC66) ≤ 1, high sensitivity C-reactive Protein (hsCRP) ≤ 1mg/dl and patient's global assessment of disease activity (PtGA) ≤ 10. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Week 12
Percentage of Participants With ACR/EULAR Remission at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) ≤ 1, Swollen Joint Count 66 (SJC66) ≤ 1, high sensitivity C-reactive Protein (CRP) ≤ 1mg/dl and patient's global assessment of disease activity (PtGA) ≤ 10.	Week 24
Percentage of Participants With ACR/EULAR Remission at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) ≤ 1, Swollen Joint Count 66 (SJC66) ≤ 1, high sensitivity C-reactive Protein (CRP) ≤ 1mg/dl and patient's global assessment of disease activity (PtGA) ≤ 10.	Week 24
Change From Baseline in DAS28-CRP and DAS28-ESR at Week 12	DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR in mm/hr (mm/hour) and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in DAS28-CRP and DAS28-ESR at Week 24 for Treatment Arms That Started Study Intervention From Day 1	DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR in mm/hr (mm/hour) and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity.	Baseline (Day 01) and Week 24
Change From Baseline in DAS28-CRP and DAS28-ESR at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR in mm/hr (mm/hour) and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity.	Baseline (Day 01) and Week 24
Change From Baseline in HAQ-DI at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the difficulty of a participant in eight domains of daily activities: Dressing & grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, Common daily activities. HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0=least difficulty to 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement.	Baseline (Day 01) and Week 24
Change From Baseline in HAQ-DI at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the difficulty of a participant in eight domains of daily activities: Dressing & grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, Common daily activities. HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0=least difficulty to 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement.	Baseline (Day 01) and Week 24
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Week 12	The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in FACIT-Fatigue at Week 24 for Treatment Arms That Started Study Intervention From Day 1	The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement.	Baseline (Day 01) and Week 24
Change From Baseline in FACIT-Fatigue at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement.	Baseline (Day 01) and Week 24
Change From Baseline in Subject-completed Medical Outcomes Study Short-Form 36 (SF-36) Physical Component Scores (PCS) at Week 12	The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The PCS is an aggregate score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. T-score scale was used for PCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall physical heath. Quality Metrics software was used for scoring for SF-36. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in SF-36 PCS at Week 24 for Treatment Arms That Started Study Intervention From Day 1	The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The PCS is an aggregate score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. T-score scale was used for PCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall physical heath. Quality Metrics software was used for scoring for SF-36.	Baseline (Day 01) and Week 24
Change From Baseline in SF-36 PCS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The PCS is an aggregate score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. T-score scale was used for PCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall physical heath. Quality Metrics software was used for scoring for SF-36.	Baseline (Day 01) and Week 24
Change From Baseline in SF-36 Mental Component Scores (MCS) at Week 12	The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in SF-36 MCS at Week 24 for Treatment Arms That Started Study Intervention From Day 1	The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36.	Baseline (Day 01) and Week 24
Change From Baseline in SF-36 MCS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36.	Baseline (Day 01) and Week 24
Change From Baseline in SF-36 Domain Scores at Week 12	The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (social functioning, vitality, mental health, and role-emotional domains) and PCS consists of 4 domains (physical functioning, role-physical, bodily pain and general health). The individual question items are first summed for each item under the various sections. Then, those domain scores are scaled between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in SF-36 Domain Scores at Week 24 for Treatment Arms That Started Study Intervention From Day 1	The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (social functioning, vitality, mental health, and role-emotional domains) and PCS consists of 4 domains (physical functioning, role-physical, bodily pain and general health). The individual question items are first summed for each item under the various sections. Then, those domain scores are scaled between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement.	Baseline (Day 01) and Week 24
Change From Baseline in SF-36 Domain Scores at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (social functioning, vitality, mental health, and role-emotional domains) and PCS consists of 4 domains (physical functioning, role-physical, bodily pain and general health). The individual question items are first summed for each item under the various sections. Then, those domain scores are scaled between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement.	Baseline (Day 01) and Week 24
Incidence of Adverse Events (AEs), Serious Adverse Event (SAEs), Adverse Events of Special Interest (AESI)	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. A SAE is any untoward medical occurrence that, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity and/or can result in death.	Up to Week 24
Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 12	Blood samples was collected for the assessment of change from baseline in hematology parameters including neutrophil, lymphocyte, platelet count. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Blood samples was collected for the assessment of change from baseline in hematology parameters including neutrophil, lymphocyte, platelet count.	Baseline (Day 01) and Week 24
Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Blood samples was collected for the assessment of change from baseline in hematology parameters including neutrophil, lymphocyte, platelet count.	Baseline (Week 12) and Week 24
Change From Baseline in White Blood Cell (WBC) Count (Giga Cells Per Liter) at Week 12	Blood samples was collected for the assessment of change from baseline in hematology parameter WBC count. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in WBC Count (Giga Cells Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Blood samples was collected for the assessment of change from baseline in hematology parameter WBC count.	Baseline (Day 01) and Week 24
Change From Baseline in WBC Count (Giga Cells Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Blood samples was collected for the assessment of change from baseline in hematology parameter WBC count.	Baseline (Week 12) and Week 24
Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 12	Blood samples was collected for the assessment of change from baseline in hematology parameter hemoglobin level. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 24 for Treatment Arms That Started Study Intervention From Day 1	Blood samples was collected for the assessment of change from baseline in in hematology parameter hemoglobin level.	Baseline (Day 01) and Week 24
Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Blood samples was collected for the assessment of change from baseline in in hematology parameter hemoglobin level.	Baseline (Week 12) and Week 24
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	Blood samples was collected for the assessment of change from baseline in laboratory parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) gamma-glutamyl transferase (GGT) levels. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in AST, ALT, AP, GGT Levels (International Units Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Blood samples was collected for the assessment of change from baseline in laboratory parameters including AST, ALT, AP, GGT levels.	Baseline (Day 01) and Week 24
Change From Baseline in AST, ALT, AP, GGT Levels (International Units Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Blood samples was collected for the assessment of change from baseline in laboratory parameters including AST, ALT, AP, GGT levels.	Baseline (Week 12) and Week 24
Change From Baseline in Albumin Level (Grams Per Liter) at Week 12	Blood samples was collected for the assessment of change from baseline in laboratory parameter albumin level. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in Albumin Level (Grams Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Blood samples was collected for the assessment of change from baseline in laboratory parameter albumin level.	Baseline (Day 01) and Week 24
Change From Baseline in Albumin Level (Grams Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Blood samples was collected for the assessment of change from baseline in laboratory parameter albumin level.	Baseline (Week 12) and Week 24
Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 12	Blood samples was collected for the assessment of change from baseline in laboratory parameter total bilirubin level. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Blood samples was collected for the assessment of change from baseline in laboratory parameter bilirubin level.	Baseline (Day 01) and Week 24
Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Blood samples was collected for the assessment of change from baseline in laboratory parameter bilirubin level.	Baseline (Week 12) and Week 24
Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 12	Blood samples was collected for the assessment of change from baseline in lipid profile of total cholesterol levels. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Blood samples was collected for the assessment of change from baseline in lipid profile of total cholesterol levels.	Baseline (Day 01) and Week 24
Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Blood samples was collected for the assessment of change from baseline in lipid profile of total cholesterol levels.	Baseline (Week 12) and Week 24
Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol (Millimoles Per Liter) at Week 12	Blood samples was collected for the assessment of change from baseline in fasting lipid profile including LDL cholesterol, HDL cholesterol levels. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in Fasting Lipid Profile: LDL Cholesterol, HDL Cholesterol (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Blood samples was collected for the assessment of change from baseline in fasting lipid profile including LDL cholesterol, HDL cholesterol levels.	Baseline (Day 01) and Week 24
Change From Baseline in Fasting Lipid Profile: LDL Cholesterol, HDL Cholesterol (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Blood samples was collected for the assessment of change from baseline in fasting lipid profile including LDL cholesterol, HDL cholesterol levels.	Baseline (Week 12) and Week 24
Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 12	Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1	Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels.	Baseline (Day 01) and Week 24
Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels.	Baseline (Week 12) and Week 24
Number of Participants With National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) >=Grade 3 Hematological/Clinical Chemistry Abnormalities for Treatment Arms That Started Study Intervention From Day 1	Number of participants who reported NCI-CTCAE Grade 3 or higher for hematological and clinical chemistry abnormalities were summarized.	Up to Week 24
Concentrations of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) Autoantibody	Blood samples were collected for markers which may influence rheumatoid arthritis. Concentrations of GM-CSF autoantibodies was determined.	At baseline
Number of Participants With Anti-GSK3196165 Antibodies	Blood samples were collected for anti-GSK3196165 antibodies detection assay using tiered testing schema: screening, confirmation and titration steps was used for immunogenicity analysis.	Up to Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline 4-beta-hydroxy Cholesterol, Cholesterol at (Millimoles Per Liter) Week 12	Blood samples was collected for the assessment of change from baseline in lipid profile parameter including 4-beta-hydroxycholesterol, cholesterol levels. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.	Baseline (Day 01) and Week 12
Change From Baseline 4-beta-hydroxy Cholesterol, Cholesterol at (Millimoles Per Liter) Week 24 for Treatment Arms That Started Study Intervention From Day 1	Blood samples was collected for the assessment of change from baseline in lipid profile parameter including 4-beta-hydroxycholesterol, cholesterol levels.	Baseline (Day 01) and Week 24
Change From Baseline 4-beta-hydroxy Cholesterol, Cholesterol at (Millimoles Per Liter) Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12	Blood samples was collected for the assessment of change from baseline in lipid profile parameter including 4-beta-hydroxycholesterol, cholesterol levels.	Baseline (Week 12) and Week 24

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Iqvia Pty Ltd
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Publications and helpful links

Helpful Links

• 209564 contRAst X NCT04333147

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2019
• Primary Completion (Actual): September 15, 2021
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: October 18, 2019
• First Posted (Actual): October 22, 2019

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; GSK3196165; Otilimab; bDMARD; Sarilumab
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: 202018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No