Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

• Register: ClinicalTrials.gov
• Last refreshed on: 8 April 2024
• Main ID: NCT03980483
• Date of registration: 15/05/2019
• 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 Methotrexate contRAst 1
• 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 Methotrexate in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
• Date of first enrolment: May 16, 2019
• Target sample size: 1537
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03980483
• 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, Canada, China, Czechia, Hungary, India, Italy, Latvia, Lithuania, Malaysia, Mexico, Poland, Russian Federation, Serbia, South Africa, Spain, Ukraine, 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 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.



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

Health Condition(s) or Problem(s) studied

Arthritis, Rheumatoid

Intervention(s)

Biological: GSK3196165 (Otilimab)

Drug: Placebo

Drug: Tofacitinib 5 mg

Primary Outcome(s)

Percentage of Participants Achieving 20 Percentage (%) 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 FACIT-Fatigue at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1 [Time Frame: 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 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 24 for Placebo Switched Arms [Time Frame: Baseline (Day 1) and Week 24]

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

Change From Baseline in SF-36 MCS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in CDAI Total Score at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in SF-36 Mental Component Scores (MCS) at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

Change From Baseline in White Blood Cell (WBC) Count at Week 12 [Time Frame: 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 [Time Frame: Baseline (Day 1), 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 [Time Frame: Week 24 and Week 52]

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Percentage of Participants Achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12 [Time Frame: Week 12]

Percentage of Participants Achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: 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 [Time Frame: 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 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

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 [Time Frame: Baseline (Day 1) and Week 24]

Change From Baseline in CDAI Total Score at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

Change From Baseline in CDAI Total Score at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in Arthritis Pain VAS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in Arthritis Pain VAS at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

Change From Baseline in Arthritis Pain VAS at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 52 for Placebo Switched Arms [Time Frame: Baseline (Day 1) 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 [Time Frame: Baseline (Week 12), Week 24 and Week 52]

Change From Baseline in Clinical Chemistry Parameter of Albumin at Week 12 [Time Frame: 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 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

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 [Time Frame: Week 24 and Week 52]

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

Change From Baseline in HAQ-DI at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: 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 [Time Frame: Baseline (Week 12), Week 24 and Week 52]

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

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 [Time Frame: Baseline (Day 1) and Week 52]

Change From Baseline in Clinical Chemistry Parameter of Albumin at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Baseline (Week 12), Week 24 and Week 52]

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 24 for Treatment Arms Who Started Study Intervention From Day 1 [Time Frame: Baseline (Day 1) and Week 24]

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 24 for Placebo Switched Arms [Time Frame: Baseline (Day 1) and Week 24]

Change From Baseline in SF-36 PCS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 52 for Placebo Switched Arms [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 12 [Time Frame: 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 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Baseline (Week 12), Week 24 and Week 52]

Number of Participants Achieving ACR/EULAR Remission at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1 [Time Frame: Week 24 and Week 52]

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 52 for Placebo Switched Arms [Time Frame: 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 for Placebo Switched Arms [Time Frame: Up to Week 59]

Number of Participants Achieving ACR/EULAR Remission at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Week 24 and Week 52]

Change From Baseline in Short Form (SF)-36 Physical Component Scores (PCS) at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

Change From Baseline in FACIT-Fatigue at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: 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 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Baseline (Week 12), Week 24 and Week 52]

Change From Baseline in WBC Count at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in Van Der Heijde mTSS at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

Change From Baseline in WBC Count at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Baseline (Week 12), Week 24 and Week 52]

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 24 for Treatment Arms Who Started Study Intervention From Day 1 [Time Frame: 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 [Time Frame: Baseline (Day 1) and Week 52]

Number of Participants Achieving ACR/EULAR Remission at Week 12 [Time Frame: Week 12]

Percentage of Participants Achieving 20% Improvement in ACR20 at Week 24 (Non-Inferiority Versus Tofacitinib) [Time Frame: Week 24]

Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Week 24 and Week 52]

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 [Time Frame: 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 [Time Frame: Week 24 and Week 52]

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 [Time Frame: Week 24 and Week 52]

Number 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 SF-36 Domain Scores at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Percentage of Participants Achieving a Good/Moderate EULAR Response at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Week 24 and Week 52]

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 24 for Placebo Switched Arms [Time Frame: Baseline (Day 1) and Week 24]

Percentage of Participants Achieving ACR20/50/70 at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Week 24 and Week 52]

Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 12 [Time Frame: Week 12]

Percentage of Participants Achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 [Time Frame: Week 12]

Change From Baseline in SF-36 Domain Scores at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

Change From Baseline in SF-36 MCS at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Baseline (Day 1), Week 24 and Week 52]

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 [Time Frame: Week 12]

Number of Participants With Anti-GSK3196165 Antibodies [Time Frame: Up to Week 59]

Percentage of Participants Achieving a Good/Moderate (European League Against Rheumatism) EULAR Response at Week 12 [Time Frame: Week 12]

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 [Time Frame: Week 24 and Week 52]

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) [Time Frame: Up to Week 59]

Percentage of Participants Achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Week 24 and Week 52]

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 [Time Frame: Week 24 and Week 52]

Percentage of Participants Achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 [Time Frame: 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 [Time Frame: Week 24 and Week 52]

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) for Placebo Switched Arms [Time Frame: Up to Week 59]

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 [Time Frame: Week 24 and Week 52]

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 [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 [Time Frame: Week 12]

Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin at Week 12 [Time Frame: 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 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in Hematology Parameter of Hemoglobin at Week 12 [Time Frame: 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 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes at Week 12 [Time Frame: Baseline (Day 1) and Week 12]

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 52 for Treatment Arms Who Started Study Intervention From Day 1 [Time Frame: Baseline (Day 1) 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 [Time Frame: 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 [Time Frame: Baseline (Day 1), Week 24 and Week 52]

Concentrations of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) Autoantibody [Time Frame: At baseline]

Percentage of Participants Achieving 50%/70% Improvement in American College of Rheumatology Criteria (ACR50/70) at Week 12 [Time Frame: Week 12]

Percentage of Participants Achieving CDAI Total Score <=10 (CDAI LDA) at Week 24 and Week 52 for Placebo Switched Arms [Time Frame: Week 24 and Week 52]

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 [Time Frame: Week 12]

Secondary ID(s)

201790

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Iqvia Pty Ltd

Results

• Results available: Yes
• Date Posted: 25/10/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03980483