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NCT04333147: contRAst X

Long-term Safety and Efficacy of GSK3196165 (Otilimab) in the Treatment of Rheumatoid Arthritis (RA)

Terminated Phase 3 Results posted Last updated 7 February 2024
What this trial tests

Phase 3 trial testing Otilimab (GSK3196165) in Arthritis, Rheumatoid in 2,916 participants. Terminated before completion.

Timeline
12 May 2020
Primary endpoint
24 February 2023
24 February 2023

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment2,916
Start date12 May 2020
Primary completion24 February 2023
Estimated completion24 February 2023
Sites375 locations across Colombia, Japan, Malaysia, Poland, South Korea, Russia, Belgium, Estonia

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.

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) Primary · Up to approximately 145 Weeks

An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. Protocol defined AESIs were included.

Participants with AEs
GroupValue95% CI
Otilimab 90 mg902
Otilimab 150 mg931
Participants with SAEs
GroupValue95% CI
Otilimab 90 mg123
Otilimab 150 mg114
Participants with AESI
GroupValue95% CI
Otilimab 90 mg120
Otilimab 150 mg95
Change From Baseline in Hematology Parameter of Platelet Count at Week 24 Primary · Baseline (Day 01) and Week 24

Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.

GroupValue95% CI
Otilimab 90 mg-11.9± 66.86
Otilimab 150 mg-9.7± 66.82
Change From Baseline in Hematology Parameter of Platelet Count at Week 48 Primary · Baseline (Day 01) and Week 48

Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.

GroupValue95% CI
Otilimab 90 mg-12.5± 66.47
Otilimab 150 mg-7.6± 71.36
Change From Baseline in Hematology Parameter of Platelet Count at Week 96 Primary · Baseline (Day 01) and Week 96

Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.

GroupValue95% CI
Otilimab 90 mg-13.8± 60.72
Otilimab 150 mg-5.7± 72.81
Change From Baseline in Hematology Parameter of Platelet Count at Week 144 Primary · Baseline (Day 01) and Week 144

Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.

GroupValue95% CI
Otilimab 90 mg17.0± NA
Otilimab 150 mg-37.5± 40.31
Change From Baseline in Hematology Parameter of Hemoglobin at Week 24 Primary · Baseline (Day 01) and Week 24

Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.

GroupValue95% CI
Otilimab 90 mg0.4± 10.10
Otilimab 150 mg0.3± 9.89
Change From Baseline in Hematology Parameter of Hemoglobin at Week 48 Primary · Baseline (Day 01) and Week 48

Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.

GroupValue95% CI
Otilimab 90 mg-0.5± 10.38
Otilimab 150 mg-1.1± 10.62
Change From Baseline in Hematology Parameter of Hemoglobin at Week 96 Primary · Baseline (Day 01) and Week 96

Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.

GroupValue95% CI
Otilimab 90 mg1.0± 11.37
Otilimab 150 mg1.2± 10.24
Change From Baseline in Hematology Parameter of Hemoglobin at Week 144 Primary · Baseline (Day 01) and Week 144

Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.

GroupValue95% CI
Otilimab 90 mg-1.0± NA
Otilimab 150 mg2.0± 2.83
Change From Baseline in White Blood Cell (WBC) Count With Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 24 Primary · Baseline (Day 01) and Week 24

Blood samples were collected for the assessment of change from baseline in hematology parameters including White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils.

Neutrophils
GroupValue95% CI
Otilimab 90 mg-0.348± 2.18
Otilimab 150 mg-0.390± 2.13
Lymphocytes
GroupValue95% CI
Otilimab 90 mg-0.001± 0.55
Otilimab 150 mg-0.012± 0.55
Monocytes
GroupValue95% CI
Otilimab 90 mg0.003± 0.18
Otilimab 150 mg0.00± 0.194
Eosinophils
GroupValue95% CI
Otilimab 90 mg0.027± 0.1623
Otilimab 150 mg0.022± 0.171
Basophils
GroupValue95% CI
Otilimab 90 mg-0.001± 0.0405
Otilimab 150 mg-0.001± 0.04
Total WBC
GroupValue95% CI
Otilimab 90 mg-0.32± 2.212
Otilimab 150 mg-0.38± 2.230
Change From Baseline in White Blood Cell (WBC) Count With Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 48 Primary · Baseline (Day 01) and Week 48

Blood samples were collected for the assessment of change from baseline in hematology parameters including White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils.

Neutrophils
GroupValue95% CI
Otilimab 90 mg-0.318± 2.2215
Otilimab 150 mg-0.541± 2.1426
Lymphocytes
GroupValue95% CI
Otilimab 90 mg-0.022± 0.5385
Otilimab 150 mg-0.051± 0.5725
Monocytes
GroupValue95% CI
Otilimab 90 mg-0.002± 0.1871
Otilimab 150 mg-0.013± 0.2461
Eosinophils
GroupValue95% CI
Otilimab 90 mg0.018± 0.1435
Otilimab 150 mg0.028± 0.1844
Basophils
GroupValue95% CI
Otilimab 90 mg-0.004± 0.0391
Otilimab 150 mg-0.006± 0.0403
Total WBC
GroupValue95% CI
Otilimab 90 mg-0.33± 2.283
Otilimab 150 mg-0.58± 2.262
Change From Baseline in White Blood Cell (WBC) Count With Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 96 Primary · Baseline (Day 01) and Week 96

Blood samples were collected for the assessment of change from baseline in hematology parameters including White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils.

Neutrophils
GroupValue95% CI
Otilimab 90 mg-0.243± 1.8851
Otilimab 150 mg-0.582± 2.4346
Lymphocytes
GroupValue95% CI
Otilimab 90 mg0.090± 0.6453
Otilimab 150 mg0.018± 0.5816
Monocytes
GroupValue95% CI
Otilimab 90 mg-0.042± 0.2001
Otilimab 150 mg-0.001± 0.2035
Eosinophils
GroupValue95% CI
Otilimab 90 mg0.025± 0.1725
Otilimab 150 mg0.029± 0.1526
Basophils
GroupValue95% CI
Otilimab 90 mg-0.007± 0.0423
Otilimab 150 mg-0.013± 0.0346
Total WBC
GroupValue95% CI
Otilimab 90 mg-0.18± 2.043
Otilimab 150 mg-0.53± 2.568

Adverse events — posted to ClinicalTrials.gov

Time frame: All AE and SAE were collected from the start of the study intervention. Initially the study was planned for 4 years approx. 208 weeks however due to early termination by sponsor; data for all Adverse event was collected up to approximately 145 Weeks only.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Otilimab 90 mg
Serious: 123/1456 (8%)
Deaths: 10/1456
Otilimab 150 mg
Serious: 114/1459 (8%)
Deaths: 9/1459

Serious adverse events (187 terms)

ReactionSystemOtilimab 90 mgOtilimab 150 mg
COVID-19 pneumoniaInfections and infestations
OsteoarthritisMusculoskeletal and connective tissue disorders
Rheumatoid arthritisMusculoskeletal and connective tissue disorders
PneumoniaInfections and infestations
COVID-19Infections and infestations
Acute myocardial infarctionCardiac disorders
Myocardial infarctionCardiac disorders
CellulitisInfections and infestations
Femoral neck fractureInjury, poisoning and procedural complications
Femur fractureInjury, poisoning and procedural complications
Transient ischaemic attackNervous system disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Atrial fibrillationCardiac disorders
Coronary artery diseaseCardiac disorders
DiverticulumGastrointestinal disorders
Gastric ulcerGastrointestinal disorders
GastritisGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
PyrexiaGeneral disorders
Sudden deathGeneral disorders
CholelithiasisHepatobiliary disorders
PeritonitisInfections and infestations
Postoperative wound infectionInfections and infestations
SepsisInfections and infestations
UrosepsisInfections and infestations
Other adverse events (3 terms — click to expand)

ReactionSystemOtilimab 90 mgOtilimab 150 mg
COVID-19Infections and infestations
Rheumatoid arthritisMusculoskeletal and connective tissue disorders
Upper respiratory tract infectionInfections and infestations

Most-reported serious reactions: COVID-19 pneumonia, Osteoarthritis, Rheumatoid arthritis, Pneumonia, COVID-19, Acute myocardial infarction, Myocardial infarction, Cellulitis.

Data from ClinicalTrials.gov NCT04333147 adverse events section.

Sponsor's own description

RA is a chronic, systemic inflammatory autoimmune disease which requires treatment for a long time period, hence it is important to study the long-term safety and efficacy of the continuous treatment with GSK3196165 over several years. This is a Phase 3, multicenter, parallel group treatment and long-term extension study primarily to assess safety with efficacy assessment as a secondary objective. Adult participants with RA who have completed the treatment phase of a qualifying GSK3196165 clinical studies (Phase 3 studies contRAst 1 (201790: NCT03980483), contRAst 2 (201791: NCT03970837) and contRAst 3 (202018: NCT04134728) and who, in investigator's judgement will benefit from extended treatment with GSK3196165 will be included in this study (contRAst X \[209564: NCT04333147\]). Participants will continue to receive the same background conventional synthetic disease modifying anti-rheumatic drug(s) \[csDMARD(s)\] treatment as they received in their qualifying study. Eligible participants will be enrolled to receive weekly GSK3196165 90 milligrams (mg) or 150 mg by subcutaneous (SC) injection. The anticipated study duration is approximately 4 years which will enable participants to receive treatment with GSK3196165 until it is expected to become commercially available. Approximately 3000 participants from the qualifying studies will participate in this long-term extension study

Publications & conference data

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

  1. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  2. 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
  3. 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
  4. 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
  5. Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2).
    Fleischmann RM, van der Heijde D, Strand V, Atsumi T, et al · · 2023 · cited 24× · PMID 37699654 · DOI 10.1136/ard-2023-224482
  6. Anti-GM-CSF otilimab versus sarilumab or placebo in patients with rheumatoid arthritis and inadequate response to targeted therapies: a phase III randomised trial (contRAst 3).
    Taylor PC, Weinblatt ME, McInnes IB, Atsumi T, et al · · 2023 · cited 20× · PMID 37696589 · DOI 10.1136/ard-2023-224449
  7. Immunomodulatory Therapeutic Proteins in COVID-19: Current Clinical Development and Clinical Pharmacology Considerations.
    Ji P, Chen J, Golding A, Nikolov NP, et al · · 2020 · cited 6× · PMID 32779201 · DOI 10.1002/jcph.1729
  8. Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X).
    Weinblatt ME, Taylor PC, McInnes IB, Atsumi T, et al · · 2025 · cited 2× · PMID 40044198 · DOI 10.1136/bmjopen-2024-088869

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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/NCT04333147.

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