Phase 3
N=527
A Moderate to Severe Rheumatoid Arthritis Study
Rheumatoid Arthritis
Bottom Line
View on ClinicalTrials.gov: NCT01721044 ↗Enrolled (actual)
527
Serious AEs
6.4%
Results posted
Jan 2018
Primary outcome: Primary: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response - Placebo Versus Baricitinib 4 mg — 27.3; 55.4 Percentage of Participants — p=0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Placebo (Drug); Baricitinib (Drug); cDMARD (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Eli Lilly and Company
- Primary completion
- Jun 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response - Placebo Versus Baricitinib 4 mg |
27.3; 55.4 | 0.001 sig |
| SECONDARY Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 4 mg |
-0.20; -0.42 | 0.001 sig |
| SECONDARY 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 |
-0.85; -1.81 | 0.001 sig |
| SECONDARY 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 |
1.7; 5.1 | 0.140 |
| SECONDARY Percentage of Participants Achieving ACR20 Response - Placebo Versus Baricitinib 2 mg |
27.3; 48.9 | 0.001 sig |
| SECONDARY Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 2 mg |
-0.20; -0.38 | 0.001 sig |
| SECONDARY Change From Baseline in the DAS28 - hsCRP - Placebo Versus Baricitinib 2 mg |
-0.85; -1.53 | 0.001 sig |
| SECONDARY Percentage of Participants Achieving ACR/EULAR Remission - SDAI ≤3.3 - Placebo Versus Baricitinib 2 mg |
1.7; 2.3 | 0.723 |
| SECONDARY Percentage of Participants Achieving ACR20 Response |
27.3; 44.8; 46.3 | 0.001 sig |
| SECONDARY Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response |
8.0; 20.1; 28.2; 13.1; 23.0; 29.4 | 0.001 sig |
| SECONDARY Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response |
2.3; 12.6; 11.3; 3.4; 13.2; 16.9 | 0.002 sig |
| SECONDARY Change From Baseline in DAS28 - Erythrocyte Sedimentation Rate (ESR) |
-0.92; -1.52; -1.80 | 0.001 sig |
| SECONDARY Change From Baseline in Clinical Disease Activity Index Score |
-12.19; -17.17; -20.30 | 0.001 sig |
| SECONDARY Change From Baseline in Measures of SDAI Score |
-12.07; -17.80; -21.26 | 0.001 sig |
| SECONDARY Percentage of Participants Achieving ACR/EULAR Remission - Boolean Remission |
1.1; 4.0; 6.8 | 0.012 sig |
| SECONDARY Change From Baseline in Duration of Participant Reported Outcome - Morning Joint Stiffness |
-8.0; -25.5; -27.0 | 0.002 sig |
| SECONDARY Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS) |
-1.1; -1.8; -2.0 | 0.001 sig |
| SECONDARY Change From Baseline in Worst Joint Pain NRS |
-1.2; -2.1; -2.5 | 0.001 sig |
| SECONDARY Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores |
5.9; 8.8; 8.5; 6.6; 8.8; 9.7 | 0.005 sig |
| SECONDARY 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) |
1.6; 3.4; 2.4; 2.5; 3.2; 3.3 | 0.448 |
| SECONDARY Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores |
0.035; 0.080; 0.128; 0.042; 0.082; 0.128 | 0.001 sig |
| SECONDARY Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores |
3.2; -6.7; -6.5; 0.9; -1.9; -2.3 | 0.362 |
| SECONDARY Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib |
65.6; 130 | — |
| SECONDARY Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib |
615; 1140 | — |
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).
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
- Have experienced any of the following within 12 weeks of study entry: myocardial infarction, unstable ischemic heart disease, stroke, or have New York Heart Association stage IV heart failure
- Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data
- Are largely or wholly incapacitated permitting little or no self care, such as, being bedridden or confined to a wheelchair
- Have an estimated glomerular filtration rate (eGFR) based on the most recent available serum creatinine using the Modification of Diet in Renal Disease (MDRD) method of 1.5 times the ULN or the most recent available total bilirubin ≥1.5 times the ULN
- Have a history of, lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative dis
Data sourced from ClinicalTrials.gov (NCT01721044). 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.