A Randomized, Double-Blind, Active-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib (LY3009104) in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had Limited or No Treatment With Disease-Modifying Antirheumatic Drugs
Overview
- Phase
- Phase 3
- Intervention
- Baricitinib
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Eli Lilly and Company
- Enrollment
- 588
- Locations
- 1
- Primary Endpoint
- Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to determine whether baricitinib therapy alone is noninferior to methotrexate (MTX) therapy alone in the treatment of moderate to severe active rheumatoid arthritis (RA) in those who have had limited or no treatment with MTX and are naive to other conventional or biologic disease-modifying antirheumatic drugs (DMARDs).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have a diagnosis of adult-onset rheumatoid arthritis (RA) as defined by American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2010 Criteria for the Classification of RA
- •Have documented history of positive rheumatoid factor and/or cyclic citrullinated peptide (CCP) antibody test
- •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 ≥1.2 times the upper limit of normal (ULN)
- •Have had limited or no treatment with methotrexate (MTX)
Exclusion Criteria
- •Have received conventional disease-modifying antirheumatic drugs (DMARDs) other than MTX (eg, gold salts, cyclosporine, leflunomide, azathioprine, hydroxychloroquine, sulfasalazine or any other immunosuppressives)
- •Are currently receiving corticosteroids at doses \>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
- •Have started a new physiotherapy treatment for RA in the 2 weeks prior to study entry
- •Have ever received any biologic DMARD
- •Have received interferon therapy within 4 weeks prior to study entry or are anticipated to require interferon therapy during the study
- •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 a 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.)
Arms & Interventions
Baricitinib
Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Intervention: Baricitinib
Baricitinib + MTX
Baricitinib 4 milligram (mg) administered orally once daily through Week 52. Participants received methotrexate (MTX) orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Intervention: Baricitinib
Baricitinib + MTX
Baricitinib 4 milligram (mg) administered orally once daily through Week 52. Participants received methotrexate (MTX) orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Intervention: Methotrexate
Baricitinib + MTX
Baricitinib 4 milligram (mg) administered orally once daily through Week 52. Participants received methotrexate (MTX) orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Intervention: Folic Acid
Baricitinib
Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Intervention: MTX Placebo
Baricitinib
Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Intervention: Folic Acid
MTX
MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Intervention: Methotrexate
MTX
MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Intervention: Baricitinib Placebo
MTX
MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Intervention: Folic Acid
Outcomes
Primary Outcomes
Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)
Time Frame: Week 24
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "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 discontinued study or drug or were rescued before analysis time point were deemed non-responders.
Secondary Outcomes
- Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)(Week 52)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score(Baseline, Week 24)
- Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP)(Baseline, Week 24)
- Change From Baseline in the Modified Total Sharp Score (mTSS)(Baseline, Week 24)
- Percentage of Participants Who Achieved a Simplified Disease Activity Index (SDAI) Score ≤3.3(Week 24)
- Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response(Week 12, Week 24, Week 52)
- Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response(Week 12, Week 24, Week 52)
- Change From Baseline in Clinical Disease Activity Index (CDAI) Score(Baseline, Week 24; Baseline, Week 52)
- Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)(Baseline, Week 24; Baseline, Week 52)
- Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission(Week 12, Week 24, Week 52)
- Change From Baseline in Joint Space Narrowing and Bone Erosion Scores(Baseline, Week 24; Baseline, Week 52)
- Change From Baseline in Duration of Morning Joint Stiffness(Baseline, Week 52)
- Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS)(Baseline, Week 24; Baseline Week 52)
- Change From Baseline in Worst Joint Pain Numeric Rating Scale (NRS)(Baseline, Week 24; Baseline Week 52)
- Change From Baseline in Mental Component Score (MCS) and Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute)(Baseline, Week 24; Baseline Week 52)
- Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores(Baseline, Week 24; Baseline Week 52)
- Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health)(Baseline, Week 24; Baseline Week 52)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores(Baseline, Week 24; Baseline Week 52)
- Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores(Baseline, Week 24; Baseline Week 52)
- Population Pharmacokinetics (PK): Peak Concentration at Steady State (Cmax,ss) of Baricitinib(Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 24; Week 32; Pre-dose)
- Population PK: Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib(Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 24; Week 32; Pre-dose)