Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic (cs)/Biologic (b) Disease Modifying Anti-rheumatic Drugs (DMARDs)

• Register: ClinicalTrials.gov
• Last refreshed on: 4 September 2023
• Main ID: NCT03970837
• Date of registration: 16/05/2019
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic (cs)/Biologic (b) Disease Modifying Anti-rheumatic Drugs (DMARDs) contRAst 2
• Scientific title: A 52-week, Phase 3, Multicentre, Randomised, Double Blind, Efficacy and Safety Study, Comparing GSK3196165 With Placebo and With Tofacitinib in Combination With Conventional Synthetic DMARDs, in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic DMARDs or Biologic DMARDs
• Date of first enrolment: June 5, 2019
• Target sample size: 1764
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT03970837
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Brazil, Bulgaria, China, Colombia, Estonia, France, Germany, Hungary, Japan, Korea, Republic of, Mexico, Poland, Russian Federation, Spain, Thailand, United Kingdom, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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 one or two of the csDMARDs:

- methotrexate (MTX) 15-25 mg/week** oral or injected

- hydroxychloroquine up to 400 mg/day or chloroquine up to 250 mg/day

- sulfasalazine up to 3000 mg/day

- leflunomide up to 20 mg/day***

- bucillamine up to 100 mg/day (or up to 300 mg/day if permitted per local
requirement)

- iguratimod up to 50 mg/day

- 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.

- Concomitant use of leflunomide and methotrexate is not allowed,
for safety reasons.

Key exclusion criteria

- History of other inflammatory rheumatologic or systemic autoimmune disorder, other
than Sjögren's syndrome secondary to RA, that may confound the evaluation of the
effect of the study intervention.

- 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).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Arthritis, Rheumatoid

Intervention(s)

Drug: csDMARDs

Drug: Tofacitinib

Drug: Placebo to GSK3196165 (Otilimab)

Biological: GSK3196165 (Otilimab)

Drug: Placebo to Tofacitinib

Primary Outcome(s)

Proportion of participants achieving 20% improvement in American College of Rheumatology Criteria (ACR20) at Week 12: superiority comparison with placebo [Time Frame: Week 12]

Secondary Outcome(s)

Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 (International units per liter) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 52 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in FACIT-Fatigue at Week 24 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in Arthritis pain at Week 12 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 52 (Micromoles per liter) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in lipid profile parameter of triglycerides at Week 16 (Millimoles per liter) [Time Frame: Baseline (Day 1) and Week 16]

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 12 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in Functional assessment of chronic illness therapy (FACIT)-Fatigue at Week 12 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in SF-36 domain scores at Week 12 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 12]

Proportion of participants achieving ACR20/50/70 at Week 24 [Time Frame: Week 24]

Change from Baseline in hematology parameter of hemoglobin at Week 52 (Grams per liter) [Time Frame: Baseline (Day 1) and Week 52]

Proportion of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 [Time Frame: Week 24]

Proportion of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 [Time Frame: Week 24]

Change from Baseline in lipid profile parameter of triglycerides at Week 4 (Millimoles per liter) [Time Frame: Baseline (Day 1) and Week 4]

Change from Baseline in lipid profile parameter of triglycerides at Week 52 (Millimoles per liter) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in SF-36 domain scores at Week 52 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in Van der Heijde mTSS at Week 24 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 24]

Proportion of participants achieving a good/moderate EULAR response at Week 24 [Time Frame: Week 24]

Proportion of participants achieving CDAI total score <=10 (CDAI LDA) at Week 52 [Time Frame: Week 52]

Proportion of participants with National Cancer Institute-Common terminology criteria for adverse events) (NCI-CTCAE)>=Grade 3 hematological/clinical chemistry abnormalities [Time Frame: Up to Week 59]

Change from Baseline in Arthritis pain VAS at Week 24 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in CDAI total score at Week 52 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in clinical chemistry parameter of albumin at Week 24 (Grams per liter) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes at Week 24 (Giga cells per liter) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes at Week 52 (Giga cells per liter) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in Short form (SF)-36 physical component scores at Week 12 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 12]

Number of participants with anti-GSK3196165 antibodies [Time Frame: Up to Week 59]

Proportion of participants achieving ACR/EULAR remission at Week 52 [Time Frame: Week 52]

Proportion of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 12 [Time Frame: Week 12]

Proportion of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 [Time Frame: Week 12]

Proportion of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 [Time Frame: Week 24]

Proportion of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 52 [Time Frame: Week 52]

Proportion of participants achieving no radiographic progression at Week 52 [Time Frame: Week 52]

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 (Micromoles per liter) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in FACIT-Fatigue at Week 52 (Scores on a scale) [Time Frame: 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 4 (Millimoles per liter) [Time Frame: Baseline (Day 1) and Week 4]

Change from Baseline in lipid profile parameter of total cholesterol at Week 4 (Millimoles per liter) [Time Frame: Baseline (Day 1) and Week 4]

Change from Baseline in lipid profile parameter of total cholesterol at Week 52 (Millimoles per liter) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in SF-36 domain scores at Week 24 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 24]

Proportion of participants achieving ACR20 at Week 12: non-inferiority comparison with tofacitinib [Time Frame: Week 12]

Proportion of participants achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 [Time Frame: Week 12]

Proportion of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 52 [Time Frame: Week 52]

Proportion of participants achieving no radiographic progression at Week 24 [Time Frame: Week 24]

Change from Baseline in CDAI total score at Week 12 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in CDAI total score at Week 24 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in clinical chemistry parameter of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), Gamma-Glutamyl transpeptidase (GGT) at Week 12 (International units per liter) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in HAQ-DI at Week 24 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes at Week 12 (Giga cells per liter) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in lipid profile parameter of total cholesterol at Week 16 (Millimoles per liter) [Time Frame: Baseline (Day 1) and Week 16]

Change from Baseline in SF-36 physical component scores at Week 24 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in SF-36 physical component scores at Week 52 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in clinical chemistry parameter of albumin at Week 52 (Grams per liter) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in clinical chemistry parameter of albumin at Week 12 (Grams per liter) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in Arthritis pain VAS at Week 52 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 52 (International units per liter) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in Van der Heijde mTSS at Week 12 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in WBC count at Week 24 (Giga cells per liter) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in white blood cell (WBC) count at Week 12 (Giga cells per liter) [Time Frame: Baseline (Day 1) and Week 12]

Incidence of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) [Time Frame: Up to Week 59]

Proportion of participants achieving a good/moderate EULAR response at Week 52 [Time Frame: Week 52]

Proportion of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 [Time Frame: Week 24]

Change from Baseline in HAQ-DI at Week 52 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in SF-36 mental component scores at Week 12 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in SF-36 mental component scores at Week 52 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 52]

Concentrations of Granulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody [Time Frame: Up to Week 59]

Proportion of participants achieving a good/moderate (European league against rheumatism) EULAR response at Week 12 [Time Frame: Week 12]

Proportion of participants achieving ACR/EULAR remission at Week 12 [Time Frame: Week 12]

Proportion of participants achieving ACR/EULAR remission at Week 24 [Time Frame: Week 24]

Proportion of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12 [Time Frame: Week 12]

Proportion of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 [Time Frame: Week 24]

Proportion of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12 [Time Frame: Week 12]

Proportion of participants achieving no radiographic progression at Week 12 [Time Frame: Week 12]

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 12 (Micromoles per liter) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in HAQ-DI at Week 12 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in hematology parameter of hemoglobin at Week 24 (Grams per liter) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 16 (Millimoles per liter) [Time Frame: Baseline (Day 1) and Week 16]

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 (Millimoles per liter) [Time Frame: Baseline (Day 1) and Week 52]

Change from Baseline in Van der Heijde mTSS at Week 52 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 52]

Proportion of participants achieving ACR20/50/70 at Week 12 [Time Frame: Week 12]

Proportion of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 52 [Time Frame: Week 52]

Proportion of participants achieving Clinical disease activity index (CDAI) total score less than or equal to (<=)10 [CDAI Low disease activity (LDA)] at Week 12 [Time Frame: Week 12]

Proportion of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 52 [Time Frame: Week 52]

Change from Baseline in hematology parameter of hemoglobin at Week 12 (Grams per liter) [Time Frame: Baseline (Day 1) and Week 12]

Change from Baseline in SF-36 mental component scores at Week 24 (Scores on a scale) [Time Frame: Baseline (Day 1) and Week 24]

Change from Baseline in WBC count at Week 52 (Giga cells per liter) [Time Frame: Baseline (Day 1) and Week 52]

Proportion of participants achieving ACR20/50/70 at Week 52 [Time Frame: Week 52]

Proportion of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 52 [Time Frame: Week 52]

Proportion of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 [Time Frame: Week 24]

Secondary ID(s)

201791

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Iqvia Pty Ltd