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
1 other identifier
interventional
550
15 countries
131
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2019
131 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 18, 2019
CompletedFirst Posted
Study publicly available on registry
October 22, 2019
CompletedStudy Start
First participant enrolled
October 31, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 15, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2022
CompletedResults Posted
Study results publicly available
July 17, 2023
CompletedJuly 17, 2023
July 1, 2023
1.9 years
October 18, 2019
January 31, 2023
July 11, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (87)
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) (Versus Placebo) at Week 12
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
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
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
Week 24
Change From Baseline in CDAI Total Score at Week 12
Baseline (Day 01) and Week 12
- +82 more secondary outcomes
Other Outcomes (3)
Change From Baseline 4-beta-hydroxy Cholesterol, Cholesterol at (Millimoles Per Liter) Week 12
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
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
Baseline (Week 12) and Week 24
Study Arms (6)
GSK3196165 90 mg
EXPERIMENTALEntire 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).
GSK3196165 150 mg
EXPERIMENTALEntire treatment period (24 Weeks): GSK3196165 150 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.
Sarilumab 200 mg
ACTIVE COMPARATOREntire 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.
Placebo sequence 1
PLACEBO COMPARATORFrom 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.
Placebo sequence 2
PLACEBO COMPARATORFrom 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.
Placebo sequence 3
PLACEBO COMPARATORFrom 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.
Interventions
GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.
Sarilumab solution in PFS to be administered SC.
Placebo sterile 0.9 percentage (%) weight by volume (w/v) sodium chloride solution in vial/PFS to be administered SC.
Stable dose of csDMARD(s) as SoC.
Eligibility Criteria
You may qualify if:
- \>=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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
- Iqvia Pty Ltdcollaborator
Study Sites (131)
GSK Investigational Site
Mesa, Arizona, 85210, United States
GSK Investigational Site
Phoenix, Arizona, 85032, United States
GSK Investigational Site
Sun City, Arizona, 85351, United States
GSK Investigational Site
Tucson, Arizona, 85704, United States
GSK Investigational Site
Covina, California, 91722, United States
GSK Investigational Site
San Diego, California, 92128, United States
GSK Investigational Site
Tujunga, California, 91042, United States
GSK Investigational Site
Upland, California, 91786, United States
GSK Investigational Site
Whittier, California, 90602, United States
GSK Investigational Site
Brandon, Florida, 33511, United States
GSK Investigational Site
DeBary, Florida, 32713, United States
GSK Investigational Site
Jacksonville, Florida, 32207, United States
GSK Investigational Site
Miami, Florida, 33134, United States
GSK Investigational Site
Miami, Florida, 33155, United States
GSK Investigational Site
Miami, Florida, 33165, United States
GSK Investigational Site
Miami, Florida, 33173, United States
GSK Investigational Site
Miami Lakes, Florida, 33014, United States
GSK Investigational Site
Tampa, Florida, 33613, United States
GSK Investigational Site
Tampa, Florida, 33614, United States
GSK Investigational Site
Atlanta, Georgia, 30318, United States
GSK Investigational Site
Newnan, Georgia, 30265, United States
GSK Investigational Site
Chicago, Illinois, 60607, United States
GSK Investigational Site
Skokie, Illinois, 60076, United States
GSK Investigational Site
St Louis, Missouri, 63141, United States
GSK Investigational Site
Lincoln, Nebraska, 68516, United States
GSK Investigational Site
Lebanon, New Hampshire, 03756, United States
GSK Investigational Site
Minot, North Dakota, 58701, United States
GSK Investigational Site
Cincinnati, Ohio, 45242, United States
GSK Investigational Site
Dayton, Ohio, 45417, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73104, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73112, United States
GSK Investigational Site
Greenville, South Carolina, 29601, United States
GSK Investigational Site
Austin, Texas, 78731, United States
GSK Investigational Site
Baytown, Texas, 77521, United States
GSK Investigational Site
College Station, Texas, 77845, United States
GSK Investigational Site
Colleyville, Texas, 76034, United States
GSK Investigational Site
Houston, Texas, 77065, United States
GSK Investigational Site
Houston, Texas, 77089, United States
GSK Investigational Site
Houston, Texas, 77090, United States
GSK Investigational Site
Lubbock, Texas, 79410, United States
GSK Investigational Site
Plano, Texas, 75024, United States
GSK Investigational Site
San Antonio, Texas, 78229, United States
GSK Investigational Site
San Marcos, Texas, 78666, United States
GSK Investigational Site
The Woodlands, Texas, 77382, United States
GSK Investigational Site
Tomball, Texas, 77375, United States
GSK Investigational Site
Waco, Texas, 76710, United States
GSK Investigational Site
Ciudad Autonoma Buenos Aires, Buenos Aires, C1046AAQ, Argentina
GSK Investigational Site
Ciudad Autonoma Buenos Aires, Buenos Aires, C1417, Argentina
GSK Investigational Site
Ciudad Autonoma Buenos Aires, Buenos Aires, C1430EGF, Argentina
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, 1426, Argentina
GSK Investigational Site
La Palta, Buenos Aires, B1900AXI, Argentina
GSK Investigational Site
Mar del Plata, Buenos Aires, B7600FYK, Argentina
GSK Investigational Site
San Isidro, Buenos Aires, 1643, Argentina
GSK Investigational Site
San Nicolás de los Arroyos, Buenos Aires, B2900DMH, Argentina
GSK Investigational Site
Buenos Aires, C1426BOR, Argentina
GSK Investigational Site
Buenos Aires, C1430CKE, Argentina
GSK Investigational Site
San Juan, 5400, Argentina
GSK Investigational Site
Mons, 7000, Belgium
GSK Investigational Site
Barrie, Ontario, L4M 6L2, Canada
GSK Investigational Site
Brampton, Ontario, L6T 0G1, Canada
GSK Investigational Site
Trois-Rivières, Quebec, G8Z 1Y2, Canada
GSK Investigational Site
Brno, 638 00, Czechia
GSK Investigational Site
Brno, 65691, Czechia
GSK Investigational Site
Ostrava, 70200, Czechia
GSK Investigational Site
Prague, 128 50, Czechia
GSK Investigational Site
Prague, 148 00, Czechia
GSK Investigational Site
Prague, 150 06, Czechia
GSK Investigational Site
Uherské Hradiště, 686 01, Czechia
GSK Investigational Site
Zlín, 760 01, Czechia
GSK Investigational Site
Rendsburg, Schleswig-Holstein, 24768, Germany
GSK Investigational Site
Hamburg, D-20095, Germany
GSK Investigational Site
Magdeburg, 39120, Germany
GSK Investigational Site
Budapest, 1023, Hungary
GSK Investigational Site
Székesfehérvár, 8000, Hungary
GSK Investigational Site
Veszprém, H-8200, Hungary
GSK Investigational Site
Verona, Veneto, 37126, Italy
GSK Investigational Site
Aichi, 455-8530, Japan
GSK Investigational Site
Aichi, 457-8511, Japan
GSK Investigational Site
Aichi, 460-0001, Japan
GSK Investigational Site
Chiba, 270-2296, Japan
GSK Investigational Site
Fukuoka, 807-8555, Japan
GSK Investigational Site
Hokkaido, 060-8648, Japan
GSK Investigational Site
Hokkaido, 063-0811, Japan
GSK Investigational Site
Hyōgo, 673-1462, Japan
GSK Investigational Site
Hyōgo, 675-1392, Japan
GSK Investigational Site
Ibaraki, 312-0057, Japan
GSK Investigational Site
Kagoshima, 891-0133, Japan
GSK Investigational Site
Kanagawa, 245-8575, Japan
GSK Investigational Site
Kochi, 781-0112, Japan
GSK Investigational Site
Kumamoto, 862-0976, Japan
GSK Investigational Site
Miyagi, 980-8574, Japan
GSK Investigational Site
Nagasaki, 857-1195, Japan
GSK Investigational Site
Saitama, 359-1111, Japan
GSK Investigational Site
Tokyo, 104-8560, Japan
GSK Investigational Site
Tokyo, 142-0054, Japan
GSK Investigational Site
Klaipėda, LT-92288, Lithuania
GSK Investigational Site
Šiauliai, 76231, Lithuania
GSK Investigational Site
Bialystok, 15-879, Poland
GSK Investigational Site
Bydgoszcz, 85-168, Poland
GSK Investigational Site
Gdansk, 80-382, Poland
GSK Investigational Site
Gdynia, 81-537, Poland
GSK Investigational Site
Katowice, 40-040, Poland
GSK Investigational Site
Katowice, 40-282, Poland
GSK Investigational Site
Krakow, 30-363, Poland
GSK Investigational Site
Lodz, 90-127, Poland
GSK Investigational Site
Poznan, 60-702, Poland
GSK Investigational Site
Poznan, 60-773, Poland
GSK Investigational Site
Sochaczew, 96-500, Poland
GSK Investigational Site
Torun, 87-100, Poland
GSK Investigational Site
Warsaw, 00-465, Poland
GSK Investigational Site
Warsaw, 00-874, Poland
GSK Investigational Site
Warsaw, 01-192, Poland
GSK Investigational Site
Warsaw, 02-118, Poland
GSK Investigational Site
Wroclaw, 50-381, Poland
GSK Investigational Site
Pretoria, Gauteng, 184, South Africa
GSK Investigational Site
Durban, KwaZulu-Natal, 4319, South Africa
GSK Investigational Site
Cape Town, 7500, South Africa
GSK Investigational Site
Kempton Park, 1619, South Africa
GSK Investigational Site
Pretoria, 0002, South Africa
GSK Investigational Site
Stellenbosch, 7600, South Africa
GSK Investigational Site
Incheon, 400-711, South Korea
GSK Investigational Site
Seoul, 03722, South Korea
GSK Investigational Site
Seoul, 04763, South Korea
GSK Investigational Site
Seoul, 3080, South Korea
GSK Investigational Site
A Coruña, 15006, Spain
GSK Investigational Site
Elche, 03203, Spain
GSK Investigational Site
Santander, 39008, Spain
GSK Investigational Site
Santiago de Compostela, 15706, Spain
GSK Investigational Site
Valencia, 46010, Spain
GSK Investigational Site
Romford, Essex, RM1 3PJ, United Kingdom
GSK Investigational Site
Northwood, Middlesex, HA6 2RN, United Kingdom
Related Publications (1)
Taylor PC, Weinblatt ME, McInnes IB, Atsumi T, Strand V, Takeuchi T, Bracher M, Brooks D, Davies J, Goode C, Gupta A, Mukherjee S, O'Shea C, Saurigny D, Schifano LA, Shelton C, Smith JE, Wang M, Wang R, Watts S, Fleischmann RM. 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). Ann Rheum Dis. 2023 Dec;82(12):1527-1537. doi: 10.1136/ard-2023-224449. Epub 2023 Sep 11.
PMID: 37696589DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Double blinded
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 18, 2019
First Posted
October 22, 2019
Study Start
October 31, 2019
Primary Completion
September 15, 2021
Study Completion
February 1, 2022
Last Updated
July 17, 2023
Results First Posted
July 17, 2023
Record last verified: 2023-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- 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.
- 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 for this study will be made available via the Clinical Study Data Request site.