A Study to Determine the Safety and Efficacy of LX3305 in Subjects With Active Rheumatoid Arthritis

Study Overview
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Brief Summary
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The primary objective of this study is to determine the safety of LX3305 in a dose escalation compared with placebo over 12 weeks in subjects with active rheumatoid arthritis (RA).

Official Title
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A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Determine the Safety and Efficacy of Daily Orally Administered LX3305 in Subjects With Active Rheumatoid Arthritis (RA)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: 50 mg LX3305 QD
* Drug: 100 mg LX3305 QD
* Drug: 150 mg LX3305 QD
* Drug: 200 mg LX3305 QD
* Drug: 250 mg LX3305 QD
* Drug: 300 mg LX3305 QD
* Drug: 400 mg LX3305 QD
* Drug: 250 mg LX3305 BID
* Drug: 500 mg LX3305 QD
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects, aged 18 to 75 years Active rheumatoid arthritis (RA), class I to III (defined by the American College of Rheumatology), diagnosed at least 3 months prior to Screening Minimum of 4 swollen joints (at Screening and Day 1), minimum of 4 tender joints (at Screening and Day 1), and serum C-reactive protein (CRP) level >1.2x the upper limit of normal and/or elevated erythrocyte sedimentation rate (ESR) If receiving methotrexate (7.5 mg to 25 mg/week), subject must have been treated for at least 6 weeks prior to Screening and currently receiving a stable dose of methotrexate (MTX) with a stable route of administration, and have no plans to change MTX dose during the study Ability to give written informed consent Exclusion Criteria: Women who are pregnant or nursing RA diagnosis prior to 16 years of age (juvenile RA) Intra-articular and/or parenteral corticosteroids within 4 weeks of study Day 1 Receipt of live vaccine within 4 weeks prior to Day 1 Major surgical procedure within 8 weeks prior to Day 1 Blood donation within 4 weeks prior to Day 1 Any systemic inflammatory condition History of bleeding diathesis History of medically significant opportunistic infection History of drug or alcohol abuse within 3 years prior to Day 1 History of cancer within 5 years prior to Day 1 Presence of hepatic or biliary disease History of tuberculosis History of human immunodeficiency virus (HIV) Any clinically significant laboratory test results, in the opinion of the investigator Use of any investigational agent or participation in an investigative trial within 30 days of Day 1 Concurrent use of any biologic agent for the treatment of RA or concomitant disease modifying antirheumatoid drugs (other than MTX, hydroxychloroquine, leflunomide, and sulfasalazine - at stables doses for 8 weeks)

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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg LX3305 QD<br> | Drug: 50 mg LX3305 QD<br>* 50 mg LX3305 once daily in capsule form<br>|
| Experimental: 100 mg LX3305 QD<br> | Drug: 100 mg LX3305 QD<br>* 100 mg LX3305 once daily in capsule form<br>|
| Experimental: 150 mg LX3305 QD<br> | Drug: 150 mg LX3305 QD<br>* 150 mg LX3305 once daily in capsule form<br>|
| Experimental: 200 mg LX3305 QD<br> | Drug: 200 mg LX3305 QD<br>* 200 mg LX3305 once daily in capsule form<br>|
| Experimental: 250 mg LX3305 QD<br> | Drug: 250 mg LX3305 QD<br>* 250 mg LX3305 once daily in capsule form<br>|
| Experimental: 300 mg LX3305 QD<br> | Drug: 300 mg LX3305 QD<br>* 300 mg LX3305 once daily in capsule form<br>|
| Experimental: 400 mg LX3305 QD<br> | Drug: 400 mg LX3305 QD<br>* 400 mg LX3305 once daily in capsule form<br>|
| Experimental: 250 mg LX3305 BID<br> | Drug: 250 mg LX3305 BID<br>* 250 mg LX3305 twice daily in capsule form<br>|
| Experimental: 500 mg LX3305 QD<br> | Drug: 500 mg LX3305 QD<br>* 500 mg LX3305 once daily in capsule form<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo dosing in capsule form<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects experiencing an adverse event (AE) |  | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in absolute lymphocyte counts |  | 14 weeks | 
| Maximum observed plasma concentration |  | 14 weeks | 
| Time at which maximum observed plasma concentration occurs |  | 14 weeks | 
| Half-life of drug in plasma |  | 14 weeks | 
| Changes from baseline in global health |  | 14 weeks |