Overview

This trial is active, not recruiting.

Condition rheumatoid arthritis
Treatments placebo, adalimumab, baricitinib
Phase phase 3
Targets JAK, TNF-alpha, JAK1
Sponsor Eli Lilly and Company
Start date October 2012
End date March 2015
Trial size 1280 participants
Trial identifier NCT01710358, 13978, I4V-MC-JADV

Summary

The purpose of this study is to determine whether baricitinib is superior to placebo in the treatment of participants with moderately to severely active Rheumatoid Arthritis (RA) who have had an inadequate response to methotrexate (MTX) treatment.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Placebo Comparator)
Placebo administered orally once daily through Week 24 and placebo administered by subcutaneous (SC) injection every 2 weeks through Week 50. At Week 24, participants will be given baricitinib 4 milligram (mg) orally once daily through Week 52. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 mg orally daily through Week 52. Participants will continue to take background methotrexate (MTX) therapy throughout study.
placebo
Baricitinib placebo administered orally. Adalimumab placebo administered SC.
(Active Comparator)
Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily through Week 52. Participants will continue to take background methotrexate (MTX) therapy throughout study.
adalimumab
Administered SC
(Experimental)
Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib will continue to receive baricitinib 4 mg administered orally once daily through Week 52. Participants will continue to take background methotrexate (MTX) therapy throughout study.
baricitinib LY 3009104
Administered orally

Primary Outcomes

Measure
Proportion of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)
time frame: Week 12

Secondary Outcomes

Measure
Change from Baseline in the Modified Total Sharp Score (mTSS)
time frame: Baseline, Week 24
Change from Baseline in the Disease Activity Score based on a 28-Joint Count (DAS-28)
time frame: Baseline, Week 12
Proportion of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response
time frame: Week 12, Week 24, Week 52
Change from Baseline in Measures of Clinical Disease Activity and Severity
time frame: Baseline, up to Week 52
Change from Baseline in Patient Reported Outcomes
time frame: Baseline, up to Week 52
Change from Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) Score
time frame: Baseline, Week 12

Eligibility Criteria

Male or female participants at least 18 years old.

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 ≥6 milligram per Liter (mg/L) - Have had regular use of methotrexate (MTX) for at least the 12 weeks prior to study entry at a dose that is considered acceptable to adequately assess clinical response. - Have at least 1 joint erosion in hand, wrist, or foot joints based on radiographic interpretation by the central reader and be rheumatoid factor or anticyclic citrullinated peptide (anti-CCP) antibody positive; or have at least 3 joint erosions in hand, wrist, or foot joints based on radiographic interpretation by the central reader regardless of rheumatoid factor or anti-CCP antibody status Exclusion Criteria: - Are currently receiving corticosteroids at doses >10 mg of prednisone per day (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 MTX, hydroxychloroquine, and sulfasalazine or combination of any 3 conventional disease-modifying antirheumatic drugs (cDMARDs) - Are currently receiving or have received cDMARDs (eg, gold salts, cyclosporine, azathioprine, or any other immunosuppressives) other than MTX, hydroxychloroquine (up to 400 mg/day), or sulfasalazine (up to 3000 mg/day) within 4 weeks prior to study entry - Have received leflunomide in the 12 weeks prior to study entry have started a new physiotherapy treatment for RA in the 2 weeks prior to study entry - Have ever received any biologic disease-modifying antirheumatic drugs (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 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 any condition or contraindication for adalimumab that would preclude the participant from participating in this protocol - Have active fibromyalgia that 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 Sjögren's syndrome are not excluded) - Have a diagnosis of Felty's syndrome - Have had any major surgery within 8 weeks prior to 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 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 a history of, lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for <5 years - Have been exposed to a live vaccine within 12 weeks prior to planned randomization or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination) - Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection - Have had symptomatic herpes zoster infection within 12 weeks prior to study entry - Have a history of disseminated/complicated herpes zoster (eg, multidermatomal involvement, ophthalmic zoster, central nervous system involvement, or postherpetic neuralgia) - Are immunocompromised and, in the opinion of the investigator, are at an unacceptable risk for participating in the study - Have a history of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) - Have screening laboratory test values, including thyroid-stimulating hormone (TSH), outside the reference range for the population or investigative site that, in the opinion of the investigator, pose an unacceptable risk for the participant's participation in the study - Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator or the sponsor, are clinically significant and indicate an unacceptable risk for the participant's participation in the study - Have symptomatic herpes simplex at the time of study enrollment - Have evidence of active or latent tuberculosis (TB)

Additional Information

Official title A Randomized, Double-Blind, Placebo- and Active-Controlled, Phase 3 Study Evaluating the Efficacy and Safety of Baricitinib in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate Therapy
Trial information was received from ClinicalTrials.gov and was last updated in April 2015.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.