A Randomized, Double-blind, Placebo-controlled Clinical Study of the Oral IL-12/23 Inhibitor, STA-5326 Mesylate, Administered to Patients With Rheumatoid Arthritis to Determine Safety, Tolerability, Pharmacokinetic and Synovial Tissue Outcomes

Study Overview
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Brief Summary
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It is not fully clear how rheumatoid arthritis originates and develops, but it is understood that multiple genetic and environmental factors interact to trigger its onset. The immune system attacks the joint synovium, which damages the cartilage and bone in the joint by increasing the number of inflammatory cells and forming new blood vessels in the joint space. STA-5326 mesylate inhibits the production of IL-12 and IL-23 and therefore may inhibit Th-1 cytokine production. A reduction in the Th-1 response has the potential to minimize or eliminate joint damage caused by the immune response in rheumatoid arthritis. This study is designed to assess whether the proposed mechanism of action is associated with a reduction in inflammation in the synovium of patients who have rheumatoid arthritis.

Conditions
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Active, Moderate to Severe Rheumatoid Arthritis

Intervention / Treatment
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* Drug: STA 5326 mesylate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 years of age or older. Has a diagnosis of RA in conformance with the American College of Rheumatology (ACR) criteria for at least 6 months. Has at least one knee, wrist, or ankle that has active synovitis and is amenable to arthroscopic procedures for the acquisition of synovial tissue via biopsy. Must be taking methotrexate for a minimum of 4 months prior to Day 1, with a stable dose regimen for at least 2 months, and have plans to remain on the stable dose regimen of methotrexate for the duration of this study. If female of childbearing potential, must be neither pregnant nor breast feeding, and must have a negative pregnancy test (serum β-hCG) within 1 week of Day 1. Must be willing to use double-barrier contraception methods for the duration of the study. Exclusion Criteria: Is taking any disease-modifying anti-rheumatic drug (DMARD) other than MTX concomitantly or within 1 month prior to Day 1. A positive (≥10 mm) tuberculin (PPD) skin test, unless the patient has had prior BCG immunization or has received prior suppressive treatment such as 1 year of INH. Has received any investigational drug or experimental procedure for the treatment of RA within 3 months of Day 1 for a biologic compound or within 1 month of Day 1 for a non-biologic compound. Has any clinically significant disease (e.g., renal, hepatic, neurological, cardiovascular, pulmonary, endocrine, psychiatric, hematologic, urologic, or other acute or chronic illness) that, in the opinion of the investigator, would make the patient an unsuitable candidate for this trial.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>STA-5326 mesylate | Drug: STA 5326 mesylate<br>* STA 5326 mesylate 100mg taken orally twice a day for 8 weeks with the option to continue at the same dose and frequency for an additional 4 weeks.<br>|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Placebo taken orally twice a day for 8 weeks with the option to continue at the same dose and frequency for an additional 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

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