Moderately to severely active rheumatoid arthritis MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • are at least 18 years of age • have a diagnosis of adult-onset RA as defined by 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 (or hsCRP) measurement =1.2 times the upper limit of normal (ULN) • have had limited or no treatment with MTX Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • have received conventional 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 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 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, or active vasculitis o Patients 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 patient • 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 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, or have a history of, lymphoproliferative disease; or signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine whether baricitinib monotherapy is noninferior to MTX monotherapy in the treatment of patients with moderate to severe active RA who have had limited or no treatment with MTX and are naive to other conventional or biologic DMARDs, as assessed by the proportion of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR20) at Week 24.;Secondary Objective: • proportion of patients achieving ACR20 at Week 24 for baricitinib plus MTX versus MTX monotherapy • change from baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) score • change from baseline to Week 24 in DAS28–high-sensitivity C reactive protein (hsCRP) • change from baseline to Week 24 in structural joint damage as measured by modified Total Sharp Score (mTSS [van der Heijde method]) for baricitinib plus MTX versus MTX monotherapy • area under the curve (AUC) up to Week 24 in HAQ-DI score for baricitinib monotherapy versus MTX monotherapy • AUC up to Week 24 in DAS28-hsCRP score for baricitinib monotherapy versus MTX monotherapy ;Primary end point(s): Endpoint 1: Proportion of patients achieving ACR20 (noninferiority of baricitinib monotherapy to MTX monotherapy) ;Timepoint(s) of evaluation of this end point: Enpoint 1: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Enpoints 2 to 7: Week 24 Enpoint 8: Weeks 12 and 52 Enpoints 9 to 14: Weeks 12, 24 and 52;Secondary end point(s): Endpoint 2 - Proportion of patients achieving ACR20 (baricitinib plus MTX compared to MTX monotherapy) Endpoint 3 - Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Endpoint 4 - Change from baseline in DAS28-high-sensitivity C-reactive protein (hsCRP) Endpoint 5 - Change from baseline in Modified Total Sharp Score (mTSS [van der Heijde method]) Endpoint 6 - AUC of HAQ-DI (baricitinib monotherapy compared to MTX monotherapy) Endpoint 7 - AUC of DAS28-hsCRP (baricitinib monotherapy compared to MTX monotherapy) Endpoint 8 -Proportion of patients achieving ACR20 Endpoint 9 - Proportion of patients achieving ACR50 Endpoint 10 - Proportion of patients achieving ACR70 Endpoint 11 - Proportion of patients achieving DAS28-hsCRP =3.2 Endpoint 12 - Proportion of patients achieving DAS28- hsCRP <2.6 Endpoint 13 - Proportion of patients achieving DAS28-ESR =3.2 Endpoint 14 - Proportion of patients achieving DAS28-ESR <2.6 | — |
Countries
Argentina, Austria, Belgium, Brazil, Canada, Germany, Greece, India, Italy, Japan, Korea, Republic of, Mexico, Portugal, Russian Federation, South Africa, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Eli Lilly and Company
Outcome results
None listed