A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib (LY3009104) in Patients With Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs With Moderately to Severely Active Rheumatoid Arthritis
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Eli Lilly and Company
- Enrollment
- 684
- 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 4 milligram (mg) once daily (QD) is superior to placebo in the treatment of participants with moderately to severely active Rheumatoid Arthritis (RA) who have had inadequate response to or are intolerant to at least 1 conventional disease-modifying antirheumatic drug (cDMARD)(cDMARD-IR [inadequate response] participants) and who have not received a biologic disease-modifying antirheumatic drug (DMARD).
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) 1.2 times the upper limit of normal (ULN)
- •Have had an insufficient response or are intolerant to conventional disease-modifying antirheumatic drugs (cDMARDs) and either:
- •Have had regular use of a 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
- •For participants not receiving a cDMARD at the time of entry, the investigator will document in the participant's history that the participant had failed, was unable to tolerate, or had a contraindication to treatment with a cDMARD
Exclusion Criteria
- •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 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 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
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: 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 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 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 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% Improvement (ACR20)
Time Frame: Week 12
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 discontinue study or drug or are rescued before analysis timepoint are deemed non-responders.
Secondary Outcomes
- Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score(Baseline, Week 12)
- Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP)(Baseline, Week 12)
- Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) ≤3.3(Week 12)
- Mean Duration of Morning Joint Stiffness(MJS) in the Prior 7 Days as Collected in Electronic Daily Diaries(Week 12)
- Mean Severity of Morning Joint Stiffness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries(Week 12)
- Mean Worst Tiredness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries(Week 12)
- Mean Worst Joint Pain Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries(Week 12)
- Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response(Week 12, Week 24)
- Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response(Week 12, Week 24)
- Change From Baseline in Measures of Clinical Disease Activity Index (CDAI) Score(Baseline, Week 24)
- Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission(Week 12)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scores.(Baseline, Week 12; Baseline 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; Baseline, Week 24)
- Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores(Baseline Week 12; Baseline Week 24)
- Change From Baseline in Measures of Simplified Disease Activity Index (SDAI) Score(Baseline, Week 24)
- Change From Baseline in DAS28-Erythrocyte Sedimentation Rate (DAS28-ESR)(Baseline, Week 12)
- Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104(Week 0: 30 and 90 minutes postdose; Week 8: 1 hour postdose; Week 12, Week 20 and Week 24:predose)
- Population PK: Maximum Concentration at Steady State of Dosing (AUC,ss) of LY3009104(Week 0: 30 and 90 minutes postdose; Week 8: 1 hour postdose; Week 12, Week 20 and Week 24; predose)
- Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health)(Baseline Week 12; Baseline Week 24)
- Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores(Baseline, Week 12; Baseline, Week 24)