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

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

Official Title
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A Phase II, Randomized, Double-Blind, Parallel-Group 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 Patient With Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: MLTA3698A
* Drug: adalimumab
* Drug: leflunomide
* Drug: methotrexate
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: MLTA3698A<br>* Subcutaneous repeating dose<br>Drug: leflunomide<br>* Stable dose if not on methotrexate<br>Drug: methotrexate<br>* Stable dose if not on leflunomide<br>|
| Active Comparator: B<br> | Drug: adalimumab<br>* Subcutaneous repeating dose<br>Drug: leflunomide<br>* Stable dose if not on methotrexate<br>Drug: methotrexate<br>* Stable dose if not on leflunomide<br>Drug: placebo<br>* Subcutaneous repeating dose<br>|
| Placebo Comparator: C<br> | Drug: leflunomide<br>* Stable dose if not on methotrexate<br>Drug: methotrexate<br>* Stable dose if not on leflunomide<br>Drug: placebo<br>* Subcutaneous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 |