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NCT03980483: contRAst 1

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

Completed Phase 3 Results posted Last updated 27 March 2024
What this trial tests

Phase 3 trial testing GSK3196165 (Otilimab) in Arthritis, Rheumatoid in 1,537 participants. Completed in 16 August 2022.

Timeline
16 May 2019
Primary endpoint
15 September 2021
16 August 2022

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment1,537
Start date16 May 2019
Primary completion15 September 2021
Estimated completion16 August 2022
Sites76 locations across Italy, Russia, Malaysia, Serbia, United Kingdom, Hungary, Poland, China

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Arthritis, Rheumatoid. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Achieving 20 Percentage (%) Improvement in American College of Rheumatology Criteria (ACR20) at Week 12 Superiority Comparison With Placebo Primary · Week 12

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 whe

GroupValue95% CI
GSK3196165 90mg + MTX54.7
GSK3196165 150mg + MTX50.9
Tofacitinib 5mg + MTX63.6
Pooled Placebo42.7
Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Total Score Less Than or Equal to (<=)10 [CDAI Low Disease Activity (LDA)] at Week 12 Secondary · Week 12

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), 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). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low

GroupValue95% CI
GSK3196165 90mg + MTX20.9
GSK3196165 150mg + MTX19.8
Tofacitinib 5mg + MTX32.5
Pooled Placebo13.9
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 Secondary · Baseline (Day 1) and Week 12

Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall 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 to 3 where 0=least difficulty and 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Base

GroupValue95% CI
GSK3196165 90mg + MTX-0.46± 0.025
GSK3196165 150mg + MTX-0.38± 0.024
Tofacitinib 5mg + MTX-0.5± 0.034
Pooled Placebo-0.27± 0.034
Percentage of Participants Achieving 20% Improvement in ACR20 at Week 24 (Non-Inferiority Versus Tofacitinib) Secondary · Week 24

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 whe

GroupValue95% CI
GSK3196165 90mg + MTX63.9
GSK3196165 150mg + MTX61.3
Tofacitinib 5mg + MTX74.4
Percentage of Participants Achieving 50%/70% Improvement in American College of Rheumatology Criteria (ACR50/70) at Week 24 and ACR 20/50/70 at and Week 52 for Treatment Arms Who Started Study Intervention From Day 1 Secondary · Week 24 and Week 52

ACR20/50/70 is calculated as a 20%/50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20%/50%/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)

ACR20, Week 52
GroupValue95% CI
GSK3196165 90mg + MTX63.9
GSK3196165 150mg + MTX61.1
Tofacitinib 5mg + MTX75.8
ACR50, Week 24
GroupValue95% CI
GSK3196165 90mg + MTX31.4
GSK3196165 150mg + MTX29.1
Tofacitinib 5mg + MTX46.7
ACR50, Week 52
GroupValue95% CI
GSK3196165 90mg + MTX35.0
GSK3196165 150mg + MTX34.2
Tofacitinib 5mg + MTX48.4
ACR70, Week 24
GroupValue95% CI
GSK3196165 90mg + MTX12.5
GSK3196165 150mg + MTX10.1
Tofacitinib 5mg + MTX25.1
ACR70, Week 52
GroupValue95% CI
GSK3196165 90mg + MTX16.7
GSK3196165 150mg + MTX14.4
Tofacitinib 5mg + MTX26.9
Percentage of Participants Achieving ACR20/50/70 at Week 24 and Week 52 for Placebo Switched Arms Secondary · Week 24 and Week 52

ACR20/50/70 is calculated as a 20%/50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20%/50%/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)

ACR20, Week 24
GroupValue95% CI
Placebo + MTX and GSK3196165 90mg + MTX56.7
Placebo + MTX and GSK3196165 150mg + MTX71.2
Placebo + MTX and Tofacitinib 5mg + MTX69.9
ACR20, Week 52
GroupValue95% CI
Placebo + MTX and GSK3196165 90mg + MTX70.5
Placebo + MTX and GSK3196165 150mg + MTX67.8
Placebo + MTX and Tofacitinib 5mg + MTX84.6
ACR50, Week 24
GroupValue95% CI
Placebo + MTX and GSK3196165 90mg + MTX37.0
Placebo + MTX and GSK3196165 150mg + MTX35.0
Placebo + MTX and Tofacitinib 5mg + MTX40.7
ACR50, Week 52
GroupValue95% CI
Placebo + MTX and GSK3196165 90mg + MTX28.6
Placebo + MTX and GSK3196165 150mg + MTX42.5
Placebo + MTX and Tofacitinib 5mg + MTX50.7
ACR70, Week 24
GroupValue95% CI
Placebo + MTX and GSK3196165 90mg + MTX7.9
Placebo + MTX and GSK3196165 150mg + MTX15.0
Placebo + MTX and Tofacitinib 5mg + MTX19.6
ACR70, Week 52
GroupValue95% CI
Placebo + MTX and GSK3196165 90mg + MTX10.3
Placebo + MTX and GSK3196165 150mg + MTX20.2
Placebo + MTX and Tofacitinib 5mg + MTX25.8
Percentage of Participants Achieving CDAI Total Score <=10 (CDAI LDA) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1 Secondary · Week 24 and Week 52

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), 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). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low

Week 24
GroupValue95% CI
GSK3196165 90mg + MTX29.9
GSK3196165 150mg + MTX29.8
Tofacitinib 5mg + MTX45.9
Week 52
GroupValue95% CI
GSK3196165 90mg + MTX35.5
GSK3196165 150mg + MTX37.1
Tofacitinib 5mg + MTX51.7
Percentage of Participants Achieving CDAI Total Score <=10 (CDAI LDA) at Week 24 and Week 52 for Placebo Switched Arms Secondary · Week 24 and Week 52

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), 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). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low

Week 24
GroupValue95% CI
Placebo + MTX and GSK3196165 90mg + MTX32.9
Placebo + MTX and GSK3196165 150mg + MTX37.4
Placebo + MTX and Tofacitinib 5mg + MTX45.8
Week 52
GroupValue95% CI
Placebo + MTX and GSK3196165 90mg + MTX38.5
Placebo + MTX and GSK3196165 150mg + MTX44
Placebo + MTX and Tofacitinib 5mg + MTX52.4
Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 12 Secondary · Week 12

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), 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). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI

GroupValue95% CI
GSK3196165 90mg + MTX3.8
GSK3196165 150mg + MTX2.4
Tofacitinib 5mg + MTX5.8
Pooled Placebo1.0
Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1 Secondary · Week 24 and Week 52

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), 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). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI

Week 24
GroupValue95% CI
GSK3196165 90mg + MTX6.1
GSK3196165 150mg + MTX5.2
Tofacitinib 5mg + MTX12.1
Week 52
GroupValue95% CI
GSK3196165 90mg + MTX9.4
GSK3196165 150mg + MTX4.4
Tofacitinib 5mg + MTX15.1
Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 24 and Week 52 for Placebo Switched Arms Secondary · Week 24 and Week 52

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), 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). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI

Week 24
GroupValue95% CI
Placebo + MTX and GSK3196165 90mg + MTX4.4
Placebo + MTX and GSK3196165 150mg + MTX8.4
Placebo + MTX and Tofacitinib 5mg + MTX6.4
Week 52
GroupValue95% CI
Placebo + MTX and GSK3196165 90mg + MTX4.6
Placebo + MTX and GSK3196165 150mg + MTX9.6
Placebo + MTX and Tofacitinib 5mg + MTX11.1
Percentage of Participants Achieving 50%/70% Improvement in American College of Rheumatology Criteria (ACR50/70) at Week 12 Secondary · Week 12

ACR50/70 is calculated as a 50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 50%/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

ACR50, Week 12
GroupValue95% CI
GSK3196165 90mg + MTX23.3
GSK3196165 150mg + MTX20.0
Tofacitinib 5mg + MTX34.1
Pooled Placebo12.2
ACR70, Week 12
GroupValue95% CI
GSK3196165 90mg + MTX8.5
GSK3196165 150mg + MTX6.1
Tofacitinib 5mg + MTX13.9
Pooled Placebo3.5

Adverse events — posted to ClinicalTrials.gov

Time frame: All AEs and SAEs were collected from the start of study intervention. The Pooled Placebo collected during the timeframe Week 0 to Week 12. Placebo + MTX and GSK3196165 90 mg + MTX, Placebo + MTX and GSK3196165 150 mg + MTX, Placebo + MTX and Tofacitinib 5mg + MTX collected during the timeframe Week 12 to Week 59. GSK3196165 90 mg + MTX, GSK3196165 150 mg + MTX, Tofacitinib 5mg + MTX collected during the timeframe Week 0 to Week 59.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GSK3196165 90mg + MTX
Serious: 33/513 (6%)
Deaths: 2/513
GSK3196165 150mg + MTX
Serious: 39/510 (8%)
Deaths: 7/510
Tofacitinib 5mg + MTX
Serious: 23/273 (8%)
Deaths: 3/273
Pooled Placebo
Serious: 8/241 (3%)
Deaths: 1/241
Placebo + MTX and GSK3196165 90mg + MTX
Serious: 8/80 (10%)
Deaths: 0/80
Placebo + MTX and GSK3196165 150mg + MTX
Serious: 9/82 (11%)
Deaths: 1/82
Placebo + MTX and Tofacitinib 5mg + MTX
Serious: 5/68 (7%)
Deaths: 0/68

Serious adverse events (109 terms)

ReactionSystemGSK3196165 90mg + MTXGSK3196165 150mg + MTXTofacitinib 5mg + MTXPooled PlaceboPlacebo + MTX and GSK31961…Placebo + MTX and GSK31961…Placebo + MTX and Tofaciti…
COVID-19 pneumoniaInfections and infestations
Rheumatoid arthritisMusculoskeletal and connective tissue disorders
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
Acute myocardial infarctionCardiac disorders
DeathGeneral disorders
Abscess limbInfections and infestations
COVID-19Infections and infestations
CellulitisInfections and infestations
Septic shockInfections and infestations
OsteoarthritisMusculoskeletal and connective tissue disorders
Lung adenocarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
NeutropeniaBlood and lymphatic system disorders
PancytopeniaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Cardiac arrestCardiac disorders
Coronary artery diseaseCardiac disorders
Myocardial infarctionCardiac disorders
Meniere's diseaseEar and labyrinth disorders
VertigoEar and labyrinth disorders
Cushing's syndromeEndocrine disorders
GoitreEndocrine disorders
Optic ischaemic neuropathyEye disorders
Colitis ischaemicGastrointestinal disorders
Diverticulum intestinalGastrointestinal disorders
Other adverse events (9 terms — click to expand)

ReactionSystemGSK3196165 90mg + MTXGSK3196165 150mg + MTXTofacitinib 5mg + MTXPooled PlaceboPlacebo + MTX and GSK31961…Placebo + MTX and GSK31961…Placebo + MTX and Tofaciti…
COVID-19Infections and infestations
LymphopeniaBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
Urinary tract infectionInfections and infestations
Upper respiratory tract infectionInfections and infestations
Rheumatoid arthritisMusculoskeletal and connective tissue disorders
Latent tuberculosisInfections and infestations
AnaemiaBlood and lymphatic system disorders
NasopharyngitisInfections and infestations

Most-reported serious reactions: COVID-19 pneumonia, Rheumatoid arthritis, Pneumonia, Anaemia, Acute myocardial infarction, Death, Abscess limb, COVID-19.

Data from ClinicalTrials.gov NCT03980483 adverse events section.

Sponsor's own description

This study \[contRAst 1 (201790: NCT03980483)\] 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. Participants who, in investigator's judgement will benefit from extended treatment with GSK3196165, may be included in the long-term extension study \[contRAst X (209564: NCT04333147)\]. For those participants who do not continue into the long term-extension study, there will be an 8 week safety follow-up visit following the treatment phase.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibodies to watch in 2020.
    Kaplon H, Muralidharan M, Schneider Z, Reichert JM. · · 2020 · cited 332× · PMID 31847708 · DOI 10.1080/19420862.2019.1703531
  2. GM-CSF in inflammation.
    Hamilton JA. · · 2020 · cited 236× · PMID 31611249 · DOI 10.1084/jem.20190945
  3. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  4. Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.
    Guan F, Wang R, Yi Z, Luo P, et al · · 2025 · cited 155× · PMID 40055311 · DOI 10.1038/s41392-025-02124-y
  5. GM-CSF: A Promising Target in Inflammation and Autoimmunity.
    Lee KMC, Achuthan AA, Hamilton JA. · · 2020 · cited 112× · PMID 33150139 · DOI 10.2147/itt.s262566
  6. Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies.
    Bonaventura A, Vecchié A, Wang TS, Lee E, et al · · 2020 · cited 112× · PMID 32719685 · DOI 10.3389/fimmu.2020.01625
  7. Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications.
    Zhao J, Guo S, Schrodi SJ, He D. · · 2021 · cited 105× · PMID 34899757 · DOI 10.3389/fimmu.2021.790122
  8. Neutrophil-derived granule cargoes: paving the way for tumor growth and progression.
    Rawat K, Syeda S, Shrivastava A. · · 2021 · cited 46× · PMID 33438104 · DOI 10.1007/s10555-020-09951-1

Verify or expand the search:

Other trials of GSK3196165 (Otilimab)

Trials testing the same drug.

Other recruiting trials for Arthritis, Rheumatoid

Currently open trials in the same condition.

Other GlaxoSmithKline trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03980483.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing