Overview

This trial is active, not recruiting.

Condition rheumatoid arthritis
Treatments baricitinib, methotrexate, placebo, folic acid
Phase phase 3
Targets JAK, JAK1
Sponsor Eli Lilly and Company
Start date November 2012
End date February 2015
Trial size 550 participants
Trial identifier NCT01711359, 14062, I4V-MC-JADZ

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).

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
(Experimental)
Baricitinib 4 milligram (mg) administered orally once daily through Week 52. Participants will receive methotrexate (MTX) orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
baricitinib LY3009104
Administered orally
methotrexate
Administered orally
placebo
Baricitinib placebo administered orally once daily. MTX placebo administered orally once weekly.
folic acid
Administered orally every day
(Experimental)
Baricitinib 4 mg administered orally once daily through Week 52. Participants will receive MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
baricitinib LY3009104
Administered orally
placebo
Baricitinib placebo administered orally once daily. MTX placebo administered orally once weekly.
folic acid
Administered orally every day
(Active Comparator)
MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants will also receive baricitinib placebo orally once daily. Starting at Week 24, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
methotrexate
Administered orally
placebo
Baricitinib placebo administered orally once daily. MTX placebo administered orally once weekly.
folic acid
Administered orally every day

Primary Outcomes

Measure
Proportion of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)
time frame: Week 24

Secondary Outcomes

Measure
Change from Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score
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 24
Change from Baseline in the modified Total Sharp Score (mTSS)
time frame: Baseline, Week 24
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 Patient Reported Outcomes
time frame: Baseline, up to Week 52
Change from Baseline in Measures of Clinical Disease Activity and Severity
time frame: Baseline, up to Week 52

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 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.) - 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 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 <40 milliliter per minute per 1.73 m^2 (mL/min/1.73 m^2) - Have a history of chronic liver disease with the most recent available aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >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 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, 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, 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
Trial information was received from ClinicalTrials.gov and was last updated in February 2015.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.