Phase 3
N=549
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
Arthritis, Rheumatoid
Bottom Line
View on ClinicalTrials.gov: NCT04134728 ↗Enrolled (actual)
549
Serious AEs
4.5%
Results posted
Jul 2023
Primary outcome: Primary: Percentage of Participants With 20% Improvement in American College of Rheumatology Criteria (ACR20) at Week 12 Superiority Comparison With Placebo — 44.8; 50.7; 57.5; 37.7 Percentage of participants — p=0.2868
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- GSK3196165 (Otilimab) (Biological); Sarilumab (Biological); Placebo to GSK3196165/ Sarilumab (Drug); csDMARDs (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Sep 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With 20% Improvement in American College of Rheumatology Criteria (ACR20) at Week 12 Superiority Comparison With Placebo |
44.8; 50.7; 57.5; 37.7 | 0.2868 |
| SECONDARY Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) (Versus Placebo) at Week 12 |
-0.33; -0.41; -0.46; -0.23 | — |
| SECONDARY Percentage of Participants With Clinical Disease Activity Index (CDAI) Total Score <=10 (CDAI Low Disease Activity [LDA]) at Week 12 |
20.7; 18.2; 28.1; 14.2 | — |
| SECONDARY Percentage of Participants With CDAI Total Score <=10 (CDAI LDA) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
31.2; 30.1; 42.6 | — |
| SECONDARY Percentage of Participants With CDAI Total Score <=10 (CDAI LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
24.0; 42.0; 36.1 | — |
| SECONDARY Change From Baseline in CDAI Total Score at Week 12 |
-16.87; -17.23; -20.22; -14.86 | — |
| SECONDARY Change From Baseline in CDAI Total Score at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
-20.93; -20.75; -23.22 | — |
| SECONDARY Change From Baseline in CDAI Total Score at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
-16.84; -22.91; -20.38 | — |
| SECONDARY Change From Baseline in Arthritis Pain Visual Analogue Scale (VAS) at Week 12 |
-19.35; -21.17; -25.93; -16.73 | — |
| SECONDARY Change From Baseline in Arthritis Pain VAS at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
-25.06; -24.31; -30.62 | — |
| SECONDARY Change From Baseline in Arthritis Pain VAS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
-16.98; -32.74; -18.60 | — |
| SECONDARY Percentage of Participants With CDAI Total Score <=2.8 (CDAI Remission) at Week 12 |
2.2; 4.3; 8.7; 0.6 | — |
| SECONDARY Percentage of Participants With CDAI Total Score <=2.8 (CDAI Remission) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
7.9; 8.4; 8.3 | — |
| SECONDARY Percentage of Participants With CDAI Total Score <=2.8 (CDAI Remission) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
5.1; 13.2; 8.4 | — |
| SECONDARY Percentage of Participants With ACR20 at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
58.1; 60.5; 65.1 | — |
| SECONDARY Percentage of Participants With ACR20 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
61.2; 70.7; 55.8 | — |
| SECONDARY Percentage of Participants With 50% Improvement in American College of Rheumatology Criteria (ACR50) at Week 12 |
18.2; 22.5; 25.9; 11.5 | — |
| SECONDARY Percentage of Participants With ACR50 at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
23.6; 30.1; 42.9 | — |
| SECONDARY Percentage of Participants With ACR50 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
13.1; 41.8; 24.0 | — |
| SECONDARY Percentage of Participants With 70% Improvement in American College of Rheumatology Criteria (ACR70) at Week 12 |
5.9; 10.8; 13.3; 6.1 | — |
| SECONDARY Percentage of Participants With ACR70 at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
12.3; 13.2; 22.7 | — |
| SECONDARY Percentage of Participants With ACR70 at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
4.9; 21.4; 12.1 | — |
| SECONDARY Percentage of Participants With Disease Activity Score Using 28 Joint Count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12 |
17; 17; 40.1; 13.2 | — |
| SECONDARY Percentage of Participants With DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
26.8; 24.8; 46.9 | — |
| SECONDARY Percentage of Participants With DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
12.5; 43.1; 55.9 | — |
| SECONDARY Percentage of Participants With DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 |
13.3; 8.5; 36.2; 1.9 | — |
| SECONDARY Percentage of Participants With DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
17.4; 17.2; 45.8 | — |
| SECONDARY Percentage of Participants With DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
5.7; 33.4; 40.0 | — |
| SECONDARY Percentage of Participants With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 |
10.2; 7.2; 22.2; 1.8 | — |
| SECONDARY Percentage of Participants With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
16.2; 13.9; 32.6 | — |
| SECONDARY Percentage of Participants With DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
6.8; 26.6; 32.0 | — |
| SECONDARY Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) at Week 12 |
3.1; 5.7; 23; 0.7 | — |
| SECONDARY Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
10.8; 8.9; 29.8 | — |
| SECONDARY Percentage of Participants With DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
1.1; 10.0; 24.2 | — |
| SECONDARY Percentage of Participants With a Good/Moderate European League Against Rheumatism (EULAR) Response at Week 12 |
66.3; 68.4; 84.1; 62.9 | — |
| SECONDARY Percentage of Participants With a Good/Moderate EULAR Response at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
76.3; 71.3; 86.6 | — |
| SECONDARY Percentage of Participants With a Good/Moderate EULAR Response at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
73.3; 76.7; 83.7 | — |
| SECONDARY Percentage of Participants With ACR/EULAR Remission at Week 12 |
2; 4; 9; 0 | — |
| SECONDARY Percentage of Participants With ACR/EULAR Remission at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
6; 4; 5 | — |
| SECONDARY Percentage of Participants With ACR/EULAR Remission at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
1; 1; 1 | — |
| SECONDARY Change From Baseline in DAS28-CRP and DAS28-ESR at Week 12 |
-1.34; -1.42; -2.15; -1.08; -1.41; -1.46 | — |
| SECONDARY Change From Baseline in DAS28-CRP and DAS28-ESR at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
-1.67; -1.67; -2.38; -1.7; -1.68; -2.85 | — |
| SECONDARY Change From Baseline in DAS28-CRP and DAS28-ESR at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
-1.25; -2.08; -2.15; -1.28; -1.94; -2.47 | — |
| SECONDARY Change From Baseline in HAQ-DI at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
-0.39; -0.45; -0.48 | — |
| SECONDARY Change From Baseline in HAQ-DI at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
-0.27; -0.62; -0.32 | — |
| SECONDARY Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Week 12 |
5.5; 6.8; 7.3; 5.45 | — |
| SECONDARY Change From Baseline in FACIT-Fatigue at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
6.55; 7.21; 7.99 | — |
| SECONDARY Change From Baseline in FACIT-Fatigue at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
5.48; 8.56; 7.21 | — |
| SECONDARY Change From Baseline in Subject-completed Medical Outcomes Study Short-Form 36 (SF-36) Physical Component Scores (PCS) at Week 12 |
5.08; 5.03; 5.61; 3.72 | — |
| SECONDARY Change From Baseline in SF-36 PCS at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
5.67; 5.5; 7.18 | — |
| SECONDARY Change From Baseline in SF-36 PCS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
3.76; 8.63; 4.16 | — |
| SECONDARY Change From Baseline in SF-36 Mental Component Scores (MCS) at Week 12 |
1.64; 3.45; 4.15; 1.61 | — |
| SECONDARY Change From Baseline in SF-36 MCS at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
2.22; 3.05; 3.61 | — |
| SECONDARY Change From Baseline in SF-36 MCS at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
1.44; 1.10; 2.76 | — |
| SECONDARY Change From Baseline in SF-36 Domain Scores at Week 12 |
17; 16.8; 19.8; 10.7; 6.3; 6.7 | — |
| SECONDARY Change From Baseline in SF-36 Domain Scores at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
20.7; 18.5; 23.9; 6.4; 6.7; 8.8 | — |
| SECONDARY Change From Baseline in SF-36 Domain Scores at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
15.7; 20.4; 16.9; 5.6; 3.4; 4.4 | — |
| SECONDARY Incidence of Adverse Events (AEs), Serious Adverse Event (SAEs), Adverse Events of Special Interest (AESI) |
92; 99; 98; 37; 9; 10 | — |
| SECONDARY Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 12 |
-0.039; -0.01; -0.057; 0.009; -0.255; -0.412 | — |
| SECONDARY Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
-0.079; 0.012; -0.108; -0.388; -0.422; -1.99 | — |
| SECONDARY Change From Baseline in Neutrophil, Lymphocyte, Platelet Count (Giga Cells Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
-0.030; 0.083; -0.094; -0.611; -0.643; -2.016 | — |
| SECONDARY Change From Baseline in White Blood Cell (WBC) Count (Giga Cells Per Liter) at Week 12 |
-0.29; -0.42; -1.95; -0.09 | — |
| SECONDARY Change From Baseline in WBC Count (Giga Cells Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
-0.45; -0.43; -2.15 | — |
| SECONDARY Change From Baseline in WBC Count (Giga Cells Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
-0.66; -0.60; -2.05 | — |
| SECONDARY Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 12 |
-0.9; 0.3; 5.5; -2 | — |
| SECONDARY Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
-1.9; -1; 5.8 | — |
| SECONDARY Change From Baseline in Hemoglobin Level (Grams Per Liter) Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
3.5; 0.2; 7.0 | — |
| SECONDARY Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP) Gamma-glutamyl Transferase(GGT) Levels (International Units Per Liter) at Week 12 |
0.6; 0.7; 4.5; 0.3; 0.8; -0.7 | — |
| SECONDARY Change From Baseline in AST, ALT, AP, GGT Levels (International Units Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
1.7; 2.1; 3.0; 1.6; 1.9; 6.2 | — |
| SECONDARY Change From Baseline in AST, ALT, AP, GGT Levels (International Units Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
2.5; 3.0; 0.9; 3.3; 4.2; 3.5 | — |
| SECONDARY Change From Baseline in Albumin Level (Grams Per Liter) at Week 12 |
0; 0.3; 1.6; -0.4 | — |
| SECONDARY Change From Baseline in Albumin Level (Grams Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
0.2; 0.2; 2.0 | — |
| SECONDARY Change From Baseline in Albumin Level (Grams Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
1.6; 0.5; 1.7 | — |
| SECONDARY Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 12 |
0.1; 0.4; 2.3; 0.3 | — |
| SECONDARY Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
0.1; 0.2; 2.5 | — |
| SECONDARY Change From Baseline in Total Bilirubin (Micromoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
0.8; -0.2; 1.1 | — |
| SECONDARY Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 12 |
— | — |
| SECONDARY Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
0.053; 0.061; 0.445 | — |
| SECONDARY Change From Baseline in Total Cholesterol (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
0.126; -0.006; 0.731 | — |
| SECONDARY Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol (Millimoles Per Liter) at Week 12 |
— | — |
| SECONDARY Change From Baseline in Fasting Lipid Profile: LDL Cholesterol, HDL Cholesterol (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
0.044; 0.051; 0.063; -0.026; 0.021; 0.334 | — |
| SECONDARY Change From Baseline in Fasting Lipid Profile: LDL Cholesterol, HDL Cholesterol (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
0.049; 0.000; 0.107; 0.041; 0.006; 0.513 | — |
| SECONDARY Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 12 |
— | — |
| SECONDARY Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 24 for Treatment Arms That Started Study Intervention From Day 1 |
0.075; -0.038; 0.103 | — |
| SECONDARY Change From Baseline in Fasting Lipid Profile Triglycerides (Millimoles Per Liter) at Week 24 for Placebo Switched Arms That Started Study Intervention From Week 12 |
0.072; -0.024; 0.243 | — |
| SECONDARY Number of Participants With National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) >=Grade 3 Hematological/Clinical Chemistry Abnormalities for Treatment Arms That Started Study Intervention From Day 1 |
1; 2; 1; 0; 0; 0 | — |
| SECONDARY Concentrations of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) Autoantibody |
334.008; 417.378; 250.015; 237.1; 330.527; 142.446 | — |
| SECONDARY Number of Participants With Anti-GSK3196165 Antibodies |
4; 2; 0; 1; 0; 0 | — |
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).
Eligibility 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 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.
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.
- Has known infection with human immunodeficiency virus (HIV) or current acute or chronic hepatitis B and/or hepatitis C.
Data sourced from ClinicalTrials.gov (NCT04134728). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.