Study of LX3305 in Subjects With Active Rheumatoid Arthritis on Stable Methotrexate

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the safety, tolerability, and effectiveness of LX3305 versus a placebo control in subjects with active rheumatoid arthritis on stable methotrexate therapy.

Official Title
-----------------
A Phase 2, Multi-center, Randomized, Double Blind, Placebo-controlled, Multiple-dose Study to Determine the Safety and Efficacy of Daily Orally Administered LX3305 in Subjects With Active Rheumatoid Arthritis (RA) on Stable Methotrexate (MTX) Therapy

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Drug: LX3305 low dose
* Drug: LX3305 mid dose
* Drug: LX3305 high dose
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females aged 18-75 years old Rheumatoid arthritis present for at least 6 months, functional class I, II, or III as defined by ACR criteria Active disease as determined by the presence of ≥6 swollen joints, ≥6 tender joints, and serum C-reactive protein level > upper limit of normal Receiving stable dose of MTX (≥10 mg/wk) and folate supplementation at least 8 weeks prior to Day 1 Ability to provide written informed consent Exclusion Criteria: RA diagnosis prior to 16 years of age (Juvenile RA) Lack of response to >3 disease modifying anti-rheumatic drugs (DMARDs) or exposure to >1 biologic DMARD Use of DMARDs other than MTX within 12 weeks prior to Day 1 Intra-articular and/or parenteral corticosteroids within 4 weeks prior to study Day 1 Blood donation or receipt of live vaccine within 4 weeks prior to Day 1 Major surgical procedure within 8 weeks prior to Day 1 Any systemic inflammatory condition, recurrent infection, or current infection other than onychomycosis 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)

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose<br>A low dose of LX3305; daily oral intake for 12 weeks | Drug: LX3305 low dose<br>* A low dose of LX3305; daily oral intake for 12 weeks<br>|
| Experimental: Mid Dose<br>A mid dose of LX3305; daily oral intake for 12 weeks | Drug: LX3305 mid dose<br>* A mid dose of LX3305; daily oral intake for 12 weeks<br>|
| Experimental: High Dose<br>A high dose of LX3305; daily oral intake for 12 weeks | Drug: LX3305 high dose<br>* A high dose of LX3305; daily oral intake for 12 weeks<br>|
| Placebo Comparator: Placebo<br>Matching placebo dosing with daily oral intake for 12 weeks | Drug: Placebo<br>* Matching placebo dosing with daily oral intake for 12 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20 Response at Week 12 | Evaluates the efficacy of LX3305 by utilizing the American College of Rheumatology 20% response criteria (ACR20) at 12 weeks in subjects with active RA also receiving stable doses of MTX. For a response of ACR20, there had to be ≥20% improvement in swollen joint count, ≥20% improvement in painful/tender joint count, and ≥20% improvement in at least 3 of the following: subject's assessment of pain, global assessment of disease activity, assessment of physical function, or acute phase reactant (C-reactive protein or erythrocyte sedimentation rate). | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR50 Response at Week 12 | Evaluates the efficacy of LX3305 by utilizing the American College of Rheumatology 50% response criteria (ACR50) at 12 weeks in subjects with active RA also receiving stable doses of MTX. For a response of ACR50, there had to be ≥50% improvement in swollen joint count, ≥50% improvement in painful/tender joint count, and ≥50% improvement in at least 3 of the following: subject's assessment of pain, global assessment of disease activity, assessment of physical function, or acute phase reactant (C-reactive protein or erythrocyte sedimentation rate). | Baseline and 12 weeks | 
| ACR70 Response at Week 12 | Evaluates the efficacy of LX3305 by utilizing the American College of Rheumatology 70% response criteria (ACR70) at 12 weeks in subjects with active RA also receiving stable doses of MTX. For a response of ACR70, there had to be ≥70% improvement in swollen joint count, ≥70% improvement in painful/tender joint count, and ≥70% improvement in at least 3 of the following: subject's assessment of pain, global assessment of disease activity, assessment of physical function, or acute phase reactant (C-reactive protein or erythrocyte sedimentation rate). | Baseline and 12 weeks | 
| Hybrid ACR Response at Week 12 | Evaluates the improvement in active RA by combining elements of the ACR20/50/70 with a continuous score of the mean change in core set measures. The percentage improvement from baseline was computed in each of the components of the ACR. The average percent improvement was calculated and used with the subject's ACR20, ACR50, and ACR70 status to compute the hybrid ACR response, with a positive change indicating improvement. | Baseline and 12 weeks | 
| Change From Baseline in C-reactive Protein (mg/L) at Week 12 | The C-reactive protein value (mg/L) at baseline was subtracted from the value for each of the treatment groups at Week 12. | Baseline and 12 weeks | 
| Change From Baseline in Erythrocyte Sedimentation Rate (mm) at Week 12 | The value for Erythrocyte Sedimentation Rate (mm) at baseline was subtracted from the value for each of the treatment groups at Week 12. | Baseline and 12 weeks |