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
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
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
Observational study model:
Not applicable
Primary completion date:
2021-15-09
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:
- >=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.
Key inclusion criteria
Trial location(s)
Location
GSK Investigational Site
Kenilworth, Warwickshire, United Kingdom, CV8 1JD
Status
Study Complete
Location
GSK Investigational Site
Northwood, Middlesex, United Kingdom, HA6 2RN
Status
Study Complete
Location
GSK Investigational Site
Seremban, Negeri Sembilan, Malaysia, 70300
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina, C1430EGF
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1046AAQ
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1426BOR
Status
Study Complete
Location
GSK Investigational Site
College Station, Texas, Unmapped, 77845
Status
Study Complete
Location
GSK Investigational Site
Daytona Beach, Florida, Unmapped, 32117
Status
Study Complete
Location
GSK Investigational Site
Greenville, South Carolina, Unmapped, 29601
Status
Study Complete
Location
GSK Investigational Site
Jacksonville, Florida, Unmapped, 32207
Status
Study Complete
Location
GSK Investigational Site
Johannesburg, Gauteng, South Africa, 2113
Status
Study Complete
Location
GSK Investigational Site
La Palta, Buenos Aires, Argentina, B1900AXI
Status
Study Complete
Location
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina, B7600FYK
Status
Study Complete
Location
GSK Investigational Site
Mexicali, Baja California Sur, Mexico, 21100
Status
Study Complete
Location
GSK Investigational Site
Oklahoma City, Oklahoma, Unmapped, 73112
Status
Study Complete
Location
GSK Investigational Site
Rosario, Santa Fe, Argentina, S2000DSV
Status
Study Complete
Location
GSK Investigational Site
San Diego, California, Unmapped, 92128
Status
Study Complete
Location
GSK Investigational Site
San Isidro, Buenos Aires, Argentina, 1643
Status
Study Complete
Location
GSK Investigational Site
Santiago Del Estero, Santiago Del Estero, Argentina, G4200DYB
Status
Study Complete
Location
GSK Investigational Site
Buenos Aires, Buenos Aires, Argentina, C1430CKE
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina, C1417
Status
Study Complete
Location
GSK Investigational Site
Fort Lauderdale, Florida, Unmapped, 33309
Status
Study Complete
Location
GSK Investigational Site
Panorama, Cape Town, South Africa, 7500
Status
Study Complete
Location
GSK Investigational Site
Romford, Essex, United Kingdom, RM1 3PJ
Status
Study Complete
Location
GSK Investigational Site
San Juan, San Juan, Argentina, J5402DIL
Status
Study Complete
Location
GSK Investigational Site
San Nicolas, Buenos Aires, Argentina, B2900DMH
Status
Study Complete
Location
GSK Investigational Site
Trois-Rivieres, Québec, Canada, G8Z 1Y2
Status
Study Complete
Location
GSK Investigational Site
Uherske Hradiste, Czech Republic, 686 01
Status
Study Complete
Location
GSK Investigational Site
Umhlanga, KwaZulu- Natal, South Africa, 4319
Status
Study Complete
Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
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
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
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Additional information
209564 contRAst X NCT04333147
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