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.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

1. are at least 18 years of age
2. have a diagnosis of adult-onset RA as defined by the ACR/EULAR 2010 Criteria for the Classification of RA (Aletaha et al. 2010)
3. have moderately to severely active RA defined as the presence of at least 6/68 tender joints and at least 6/66 swollen joints
a. If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC and SJC for entry or enrollment purposes.
4. have a C-reactive protein (CRP) (or hsCRP) measurement >=6 mg/L based on the most recent data (if available)
5. have had regular use of MTX for at least the 12 weeks prior to study entry at a dose that, in accordance with local clinical practice, is considered acceptable to adequately assess clinical response. The dose of MTX must have been a stable, unchanging oral dose of 7.5 to 25 mg/week (or the equivalent injectable dose) for at least the 8 weeks prior to study entry. The dose of MTX is expected to remain stable throughout the study and may be adjusted only for safety reasons
a. For patients entering the trial on MTX doses <15 mg/week, there must be clear documentation in the medical record that higher doses of MTX were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines.
b. Local standard of care should be followed for concomitant administration of folic acid.
6. are able to read, understand, and give written informed consent

Exclusion Criteria

7. 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
8. have started treatment with NSAIDs (for which the NSAID use is intended for treatment of signs and symptoms of RA) within 2 weeks of study entry or within 6 weeks of planned randomization or have been receiving an unstable dosing regimen of NSAIDs within 2 weeks of study entry or within 6 weeks of planned randomization
9. are currently receiving concomitant treatment with MTX, hydroxychloroquine, and sulfasalazine
10. 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 8 weeks prior to study entry
a. Doses of hydroxychloroquine or sulfasalazine should be stable for at least 8 weeks prior to study entry.
b. Immunosuppression related to organ transplantation is not permitted.
11. have received leflunomide in the 12 weeks prior to study entry (or within 4 weeks prior to study entry if the standard 11 days of cholestyramine is used to washout leflunomide)
12. have started a new physiotherapy treatment for RA in the 2 weeks prior to study entry;Please refer to section 8.1.2 (Exclusion criteria) page 37 of the protocol for the complete list.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of the study is to determine whether baricitinib is<br /><br>superior to placebo in the treatment of patients with moderately to severely<br /><br>active RA despite MTX treatment (ie, MTX IR), as assessed by the proportion of<br /><br>patients achieving ACR20 at Week 12.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The major secondary objectives of the study are to evaluate the efficacy of<br /><br>baricitinib versus placebo or adalimumab as assessed by:<br /><br>• change from baseline to Week 24 in structural joint damage as measured by<br /><br>modified Total Sharp Score (mTSS [van der Heijde method]) compared to placebo<br /><br>• change from baseline to Week 12 in Health Assessment Questionnaire-Disability<br /><br>Index (HAQ-DI) score compared to placebo<br /><br>• change from baseline to Week 12 in DAS28-high-sensitivity C-reactive protein<br /><br>(hsCRP) compared to placebo<br /><br><br /><br>Please refer to section 6.2 (Secondary Objectives) page 29 of the protocol for<br /><br>the complete list.</p><br>