A Study to Evaluate the Efficacy and Safety of MLTA3698A in Combination With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Compared With Adalimumab in Combination With a DMARD in Patients With Active Rheumatoid Arthritis

Phase 2

Completed

Interventions: Drug: adalimumab
Drug: MLTA3698A
Drug: leflunomide
Drug: methotrexate
Drug: placebo

Brief Summary: This is a Phase II, randomized, double-blind, placebo-controlled, parallel-group, multicenter study enrolling patients with active rheumatoid arthritis (RA).

Recruitment & Eligibility

Inclusion Criteria

Diagnosis of RA according to the 1987 revised ACR Criteria for the Classification of RA for at least 6 months prior to screening
Positive for rheumatoid factor or anti-cyclic citrullinated peptide (CCP) antibody, or both
Active disease, defined as: CRP >= 1.0 mg/dL; swollen joint count >= 6 (66 joint count); tender joint count >= 6 (68 joint count)
Previous inadequate clinical response to at least one disease-modifying anti-rheumatic drug (DMARD) consisting of either methotrexate (MTX) or leflunomide (LFU)
For patients currently receiving corticosteroids: Treatment at a stable dose during last 4 weeks prior to screening
For patients currently receiving non-steroidal anti-inflammatory drugs (NSAIDs): Treatment at a stable dose during last 4 weeks prior to screening
For patients currently receiving sulfasalazine or anti-malarials: Treatment initiated and continued for at least the last 6 months prior to screening and on a stable dose
For patients of reproductive potential (males and females): Willing to use a highly effective birth control method for the duration of the study according to local guidelines

Exclusion Criteria

Pregnant, planning to become pregnant during the study, or breastfeeding
Clinically significant abnormal laboratory values or abnormal ECG or vital signs
History of anaphylactic reactions
Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome), however patients with secondary Sjogren's syndrome are eligible for the study
History of or current inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthritis, Lyme disease) or other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome)
Current or recent (within 4 weeks prior to screening) infection, including signs, symptoms or serology of any infection, including HIV, hepatitis B or C, tuberculosis
Administration of a live, attenuated vaccine within 1 month before dosing or anticipation that such a live attenuated vaccine will be required during the study
Previous treatment with anti-TNF biologics or other biologic agents, including anti-CD20-directed therapy (e.g. rituximab), anti-IL6-directed therapy (e.g. tocilizumab), or T cell-directed therapy (e.g. abatacept)

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Baseline change in disease activity, assessed as the Disease Activity Score (DAS28) and erythrocyte sedimentation rate, or DAS28-(4)-ESR	Day 85
Incidence and severity of adverse events and clinical laboratory abnormalities as a measure of safety and tolerability of MLTA3698A	Length of study (through Day 85)

Secondary Outcome Measures

Name	Time	Method
ACR20 response rate (the proportion of patients in each treatment group meeting the American College of Rheumatology 20% responder criteria [ACR20] for their average response )	Day 85
ACR70 response rate (the proportion of patients in each treatment group meeting the American College of Rheumatology 70% responder criteria [ACR70] for their average response)	Day 85
ACR50 response rate (the proportion of patients in each treatment group meeting the American College of Rheumatology 50% responder criteria [ACR50] for their average response )	Day 85
Tender joint count	Day 85
Swollen joint count	Day 85
Investigator Global Assessment of Disease Activity	Day 85
Patient Global Assessment of Pain and Disease Activity	Day 85
Health Assessment Questionnaire Disability Index	Day 85
Patient's Global Health or Short Form Health Survey (SF-36)	Day 85
European League Against Rheumatism response rate	Day 85
Serum C-reactive protein levels	Day 85
Erythrocyte sedimentation rate	Day 85