A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Evaluating the Efficacy and Safety of Baricitinib (LY3009104) in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Eli Lilly and Company
- Enrollment
- 527
- Locations
- 1
- Primary Endpoint
- Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response - Placebo Versus Baricitinib 4 mg
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to determine whether baricitinib 4 milligram (mg) once daily is superior to placebo in the treatment of participants with moderately to severely active Rheumatoid Arthritis (RA) who have had an inadequate response to a tumor necrosis factor (TNF) inhibitor, despite ongoing treatment with conventional disease-modifying antirheumatic drugs (cDMARDs).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have a diagnosis of adult-onset Rheumatoid Arthritis (RA) as defined by the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2010 Criteria for the Classification of RA
- •Have moderately to severely active RA defined as the presence of at least 6/68 tender joints and at least 6/66 swollen joints
- •Have a C-reactive protein (CRP) or high-sensitivity C-reactive protein (hsCRP) measurement ≥ (greater than or equal to) 1 times the upper limit of normal (ULN)
- •Have been treated at approved doses with at least 1 biologic tumor necrosis factor (TNF)- alpha inhibitor for at least 3 months and either:
- •experienced insufficient efficacy or loss of efficacy
- •experienced intolerance of such treatment
- •Have had regular use of at least 1 conventional disease-modifying antirheumatic drugs (cDMARD) for at least the 12 weeks prior to study entry with a continuous, nonchanging dose for at least 8 weeks prior to study entry
Exclusion Criteria
- •Have received a biologic treatment for RA within 28 days of planned randomization; have received rituximab within 6 months of planned randomization
- •Are currently receiving corticosteroids at doses \> (greater than) 10 mg per day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of study entry or within 6 weeks of planned randomization
- •Have started treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or have been receiving an unstable dosing regimen of NSAIDs within 2 weeks of study entry or within 6 weeks of planned randomization
- •Are currently receiving concomitant treatment with methotrexate (MTX), hydroxychloroquine, and sulfasalazine or combination of any 3 cDMARDs
- •Have received any parenteral corticosteroid administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization or are anticipated to require parenteral injection of corticosteroids during the study
- •Have had 3 or more joints injected with intraarticular corticosteroids or hyaluronic acid within 2 weeks prior to study entry or within 6 weeks prior to planned randomization
- •Have active fibromyalgia that, in the investigator's opinion, would make it difficult to appropriately assess RA activity for the purposes of this study
- •Have a diagnosis of any systemic inflammatory condition other than RA, such as, but not limited to juvenile chronic arthritis, spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, active vasculitis or gout (participants with secondary Sjogren's syndrome are not excluded.)
- •Have a diagnosis of Felty's syndrome
- •Have had any major surgery within 8 weeks of study entry or will require major surgery during the study that, in the opinion of the investigator in consultation with Lilly or its designee, would pose an unacceptable risk to the participant
Arms & Interventions
Placebo
Placebo administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 milligram (mg) orally once daily through Week 24. Participants will continue to take background conventional disease-modifying antirheumatic drug (cDMARD) therapy throughout study.
Intervention: Placebo
Placebo
Placebo administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 milligram (mg) orally once daily through Week 24. Participants will continue to take background conventional disease-modifying antirheumatic drug (cDMARD) therapy throughout study.
Intervention: cDMARD
Baricitinib 2 mg
Baricitinib 2 mg administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily through Week 24. Participants will continue to take background cDMARD therapy throughout study.
Intervention: Baricitinib
Baricitinib 2 mg
Baricitinib 2 mg administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily through Week 24. Participants will continue to take background cDMARD therapy throughout study.
Intervention: cDMARD
Baricitinib 4 mg
Baricitinib 4 mg administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily through Week 24. Participants will continue to take background cDMARD therapy throughout study.
Intervention: Baricitinib
Baricitinib 4 mg
Baricitinib 4 mg administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily through Week 24. Participants will continue to take background cDMARD therapy throughout study.
Intervention: cDMARD
Outcomes
Primary Outcomes
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response - Placebo Versus Baricitinib 4 mg
Time Frame: Week 12
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. ACR20 Responder is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinue study or drug or are rescued before analysis timepoint are deemed non-responders.
Secondary Outcomes
- Change From Baseline in the Disease Activity Score Based on a 28-Joint Count (DAS-28) High Sensitivity C-Reactive Protein (hsCRP) - Placebo Versus Baricitinib 4 mg(Baseline, Week 12)
- Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 4 mg(Baseline, Week 12)
- Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission - Simplified Disease Activity Index (SDAI) ≤3.3 - Placebo Versus Baricitinib 4 mg(Week 12)
- Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response(Week 12 and Week 24)
- Change From Baseline in DAS28 - Erythrocyte Sedimentation Rate (ESR)(Baseline, Week 12)
- Percentage of Participants Achieving ACR20 Response - Placebo Versus Baricitinib 2 mg(Week 12)
- Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 2 mg(Baseline, Week 12)
- Change From Baseline in the DAS28 - hsCRP - Placebo Versus Baricitinib 2 mg(Baseline, Week 12)
- Percentage of Participants Achieving ACR/EULAR Remission - SDAI ≤3.3 - Placebo Versus Baricitinib 2 mg(Week 12)
- Percentage of Participants Achieving ACR20 Response(Week 24)
- Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response(Week 12 and Week 24)
- Change From Baseline in Clinical Disease Activity Index Score(Baseline, Week 24)
- Change From Baseline in Measures of SDAI Score(Baseline, Week 24)
- Percentage of Participants Achieving ACR/EULAR Remission - Boolean Remission(Week 24)
- Change From Baseline in Duration of Participant Reported Outcome - Morning Joint Stiffness(Baseline, Week 24)
- Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS)(Baseline, Week 24)
- Change From Baseline in Worst Joint Pain NRS(Baseline, Week 24)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores(Baseline, Week 12, Week 24)
- Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute)(Baseline, Week 12, Week 24)
- Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores(Baseline, Week 12, Week 24)
- Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores(Baseline, Week 12, Week 24)
- Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib(Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose.)
- Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib(Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose.)