Last updated: 07/26/2024 09:10:07

Efficacy and safety of GSK3196165 versus placebo and tofacitinib in participants with moderately to severely active rheumatoid arthritis who have an inadequate response to methotrexatecontRAst 1

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GSK study ID
201790
See study documents
Clinicaltrials.gov ID
NCT03980483
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A 52-week, phase 3, multicentre, randomised, double blind, efficacy and safety study comparing GSK3196165 with placebo and with tofacitinib, in combination with methotrexate in participants with moderately to severely active rheumatoid arthritis who have an inadequate response to methotrexate
Trial 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Percentage of participants achieving 20 percentage (%) improvement in American College of Rheumatology Criteria (ACR20) at Week 12 superiority comparison with placebo

Timeframe: Week 12

Secondary outcomes:

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

Timeframe: Week 12

Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12

Timeframe: Baseline (Day 1) and Week 12

Percentage of participants achieving 20% improvement in ACR20 at Week 24 (Non-Inferiority versus tofacitinib)

Timeframe: Week 24

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

Timeframe: Week 24 and Week 52

Percentage of participants achieving ACR20/50/70 at Week 24 and Week 52 for placebo switched arms

Timeframe: Week 24 and Week 52

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

Timeframe: Week 24 and Week 52

Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for placebo switched arms

Timeframe: Week 24 and Week 52

Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 12

Timeframe: Week 12

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

Timeframe: Week 24 and Week 52

Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for placebo switched arms

Timeframe: Week 24 and Week 52

Percentage of participants achieving 50%/70% improvement in American College of Rheumatology Criteria (ACR50/70) at Week 12

Timeframe: Week 12

Percentage of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12

Timeframe: Week 12

Percentage of participants achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12

Timeframe: Week 12

Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Week 24 and Week 52

Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Week 24 and Week 52

Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for placebo switched arms

Timeframe: Week 24 and Week 52

Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for placebo switched arms

Timeframe: Week 24 and Week 52

Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12

Timeframe: Week 12

Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12

Timeframe: Week 12

Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Week 24 and Week 52

Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Week 24 and Week 52

Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for placebo switched arms

Timeframe: Week 24 and Week 52

Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for placebo switched arms

Timeframe: Week 24 and Week 52

Percentage of participants achieving a good/moderate (European League Against Rheumatism) EULAR response at Week 12

Timeframe: Week 12

Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Week 24 and Week 52

Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for placebo switched arms

Timeframe: Week 24 and Week 52

Number of participants achieving ACR/EULAR remission at Week 12

Timeframe: Week 12

Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Week 24 and Week 52

Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for placebo switched arms

Timeframe: Week 24 and Week 52

Percentage of participants achieving no radiographic progression (Van der Heijde modified total sharp scores (mTSS <= 0.5) at Week 12

Timeframe: Week 12

Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Week 24 and Week 52

Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for placebo switched arms

Timeframe: Week 24 and Week 52

Change from Baseline in CDAI total score at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in CDAI total score at Week 24 and Week 52 for treatment arms Who Started Study Intervention From Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in CDAI total score at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in Van der Heijde mTSS at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in HAQ-DI at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in HAQ-DI at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in Arthritis pain VAS at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in Short form (SF)-36 physical component scores (PCS) at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in SF-36 mental component scores (MCS) at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in SF-36 domain scores at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in SF-36 PCS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in SF-36 MCS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in SF-36 PCS at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in SF-36 MCS at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in Functional assessment of chronic illness therapy (FACIT)-Fatigue at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Day 1), Week 24 and Week 52

Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI)

Timeframe: Up to Week 59

Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) for placebo switched arms

Timeframe: Up to Week 59

Change from Baseline in white blood cell (WBC) count at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in WBC count at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in WBC count at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Week 12), Week 24 and Week 52

Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Week 12), Week 24 and Week 52

Change from Baseline in hematology parameter of hemoglobin at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Week 12), Week 24 and Week 52

Change from Baseline in clinical chemistry parameter of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), Gamma-Glutamyl transpeptidase (GGT) at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Week 12), Week 24 and Week 52

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Week 12), Week 24 and Week 52

Change from Baseline in clinical chemistry parameter of albumin at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1), Week 24 and Week 52

Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for placebo switched arms

Timeframe: Baseline (Week 12), Week 24 and Week 52

Change from Baseline in lipid profile parameter of total cholesterol at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1) and Week 24

Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for placebo switched arms

Timeframe: Baseline (Day 1) and Week 24

Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1) and Week 52

Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for placebo switched arms

Timeframe: Baseline (Day 1) and Week 52

Change from Baseline in lipid profile parameter of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein-cholesterol at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1) and Week 24

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for placebo switched arms

Timeframe: Baseline (Day 1) and Week 24

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1) and Week 52

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for placebo switched arms

Timeframe: Baseline (Day 1) and Week 52

Change from Baseline in lipid profile parameter of triglycerides at Week 12

Timeframe: Baseline (Day 1) and Week 12

Change from Baseline in lipid profile parameter of triglycerides at Week 24 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1) and Week 24

Change from Baseline in lipid profile parameter of triglycerides at Week 24 for placebo switched arms

Timeframe: Baseline (Day 1) and Week 24

Change from Baseline in lipid profile parameter of triglycerides at Week 52 for treatment arms who started study intervention from Day 1

Timeframe: Baseline (Day 1) and Week 52

Change from Baseline in lipid profile parameter of triglycerides at Week 52 for placebo switched arms

Timeframe: Baseline (Day 1) and Week 52

Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE) >=Grade 3 hematological/clinical chemistry abnormalities

Timeframe: Up to Week 59

Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE) >=Grade 3 hematological/clinical chemistry abnormalities for placebo switched arms

Timeframe: Up to Week 59

Concentrations of Granulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody

Timeframe: At baseline

Number of participants with anti-GSK3196165 antibodies

Timeframe: Up to Week 59

Interventions:
  • Biological/vaccine: GSK3196165 (Otilimab)
  • Drug: Tofacitinib 5 mg
  • Drug: Placebo
    • Enrollment:
    1537
    Primary completion date:
    2021-15-09
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Roy M Fleischmann, Désirée van der Heijde, Vibeke Strand, Tatsuya Atsumi, Iain B McInnes, Tsutomu Takeuchi, Peter C Taylor, Marguerite Bracher, David Brooks, John Davies, Christopher Goode, Anubha Gupta, Sumanta Mukherjee, Ciara O'Shea, Didier Saurigny, Lorrie A Schifano, Celia Shelton, Julia E Smith, Millie Wang, Reena Wang, Sarah Watts, Michael E Weinblatt. 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).. Annals of the rheumatic diseases. 2023-Sep-12; DOI : 10.1136/ard-2023-224482 PMID: 37699654
    Medical condition
    Arthritis, Rheumatoid
    Product
    Not applicable
    Collaborators
    IQVIA
    Study date(s)
    May 2019 to August 2022
    Type
    Interventional
    Phase
    3

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Key inclusion criteria
    • >=18 years of age
    Inclusion and exclusion criteria
    Inclusion criteria:

      Key inclusion criteria

      • >=18 years of age
      • Has had RA for >=6 months and was not diagnosed before 16 years of age
      • Has active disease, as defined by having both:* − >=6/68 tender/painful joint count (TJC), and − >=6/66 swollen joint count (SJC)
      • Has at least 1 bone erosion present on hand/wrist or foot radiographs
      • Has had an inadequate response to MTX, despite currently taking MTX 15–25 mg/week** oral or injected *If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC or SJC. **A lower dose of 7.5 mg/week is acceptable if reduced for reasons of intolerance to MTX or per local requirement. Key exclusion criteria
      • Has had any active and/or recurrent infections (excluding recurrent fungal infections of the nail bed) or has required management of acute or chronic infections.
      • Has received prior treatment with an antagonist of GM-CSF or its receptor or Janus kinase (JAK) inhibitors (either experimental or approved)
      • Has received prior treatment with a biologic Disease-modifying antirheumatic drug (DMARD) which has been discontinued due to an inadequate response.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Baja, Hungary, 6500
    Status
    Study Complete
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    Location
    GSK Investigational Site
    A Coruña, Spain, 15006
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Gdynia, Poland, 81-537
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Torun, Poland, 87-100
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Warszawa, Poland, 00-465
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Warszawa, Poland, 01-192
    Status
    Study Complete
    Contact us
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    Study documents

    Study report synopsis
    Available language(s): English
    Download document(s)
    Protocol
    Available language(s): English
    Download document(s)
    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2021-15-09
    Actual study completion date
    2022-16-08

    Plain language summaries

    Summary of results in plain language
    Available language(s): English, Afrikaans, Czech, French (Canadian), Hindi, Hungarian, Italian, Latvian, Lithuanian, Malay (Malaysia), Polish, Russian, Russian (Ukraine), Serbian (Latin), Sesotho, Chinese (Simplified), Spanish (Argentina), Spanish (Mexico), Spanish, Spanish (United States), Zulu
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    To view plain language summaries on trialsummaries.com click here.

    Additional information about the trial

    Participate in clinical trial
    Additional information
    209564 contRAst X NCT04333147
    Click here
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