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

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: LX3305 low dose; Drug: LX3305 mid dose; Drug: LX3305 high dose; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria
    • Lexicon Investigational Site
  • Plovdiv, Bulgaria
    • Lexicon Investigational Site
  • Ruse, Bulgaria
    • Lexicon Investigational Site
  • Sofia, Bulgaria
    • Lexicon Investigational Site
  • Veliko Tarnovo, Bulgaria
    • Lexicon Investigational Site
• Czech Republic
  • Bruntal, Czech Republic
    • Lexicon Investigational Site
  • Hlucin, Czech Republic
    • Lexicon Investigational Site
  • Sokolov, Czech Republic
    • Lexicon Investigational Site
  • Zlin, Czech Republic
    • Lexicon Investigational Site
• Hungary
  • Bekescsaba, Hungary
    • Lexicon Investigational Site
  • Budapest, Hungary
    • Lexicon Investigational Site
  • Kecskemet, Hungary
    • Lexicon Investigational Site
  • Mako, Hungary
    • Lexicon Investigational Site
  • Sopron, Hungary
    • Lexicon Investigational Site
  • Veszprem, Hungary
    • Lexicon Investigational Site
• Poland
  • Bialystok, Poland
    • Lexicon Investigational Site
  • Dzialdowo, Poland
    • Lexicon Investigational Site
  • Gdynia, Poland
    • Lexicon Investigational Site
  • Katowice, Poland
    • Lexicon Investigational Site
  • Lublin, Poland
    • Lexicon Investigational Site
  • Warszawa, Poland
    • Lexicon Investigational Site
  • Wloszczowa, Poland
    • Lexicon Investigational Site
  • Wroclaw, Poland
    • Lexicon Investigational Site
• Serbia
  • Belgrade, Serbia
    • Lexicon Investigational Site
  • Niska Banja, Serbia
    • Lexicon Investigational Site
• United States
  • Florida
    • Gainesville, Florida, United States, 32607
      • Lexicon Investigational Site
    • Orange Park, Florida, United States, 32073
      • Lexicon Investigational Site
    • Orlando, Florida, United States, 32804
      • Lexicon Investigational Site
    • Tampa, Florida, United States, 33614
      • Lexicon Investigational Site
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Lexicon Investigational Site
    • Hagerstown, Maryland, United States, 21740
      • Lexicon Investigational Site
  • Michigan
    • Kalamazoo, Michigan, United States, 49009
      • Lexicon Investigational Site
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Lexicon Investigational Site
  • North Carolina
    • Hickory, North Carolina, United States, 28601
      • Lexicon Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19152
      • Lexicon Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Lexicon Investigational Site
  • Texas
    • Dallas, Texas, United States, 75235
      • Lexicon Investigational Site
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Lexicon Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Investigators: Study Director: Joel P. Freiman, MD, MPH, Lexicon Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: May 14, 2009
• First Submitted That Met QC Criteria: May 14, 2009
• First Posted (Estimate): May 18, 2009

Study Record Updates

• Last Update Posted (Estimate): December 15, 2011
• Last Update Submitted That Met QC Criteria: November 11, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: Protocol LX3305.1-201-RA; LX3305.201, LX2931