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THU0133 Results from A Phase 2A, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Parallel-Group Study of Jnj-40346527, an Oral CSF-1R Inhibitor, in Patients with Active Rheumatoid Arthritis despite Disease-Modifying Antirheumatic Drug Therapy
  1. M.C. Genovese1,
  2. E. Hsia2,
  3. S. Belkowski2,
  4. C. Chien2,
  5. T. Masterson2,
  6. R. Thurmond3,
  7. C. Manthey2,
  8. D. Yan2,
  9. T. Ge3,
  10. A. Greenspan4
  1. 1Stanford University, Palo Alto
  2. 2Janssen Research & Development, LLC, Spring House
  3. 3Janssen Research & Development, LLC, San Diego
  4. 4Janssen Scientific Affairs, LLC, Spring House, United States

Abstract

Background JNJ-40346527, an investigational agent, is a selective inhibitor of the colony stimulating factor-1 receptor (CSF-1R) kinase and acts to inhibit macrophage survival, proliferation and differentiation. Based on current understanding of their mechanisms of action, JNJ-40346527 and traditional DMARDS may have complementary effects in reducing inflammation in rheumatoid arthritis (RA).

Objectives To assess the safety, tolerability, and efficacy of JNJ-40346527 compared with placebo (PBO) administered for 12wks to patients with active RA despite DMARD therapy.

Methods In this randomized, double-blind, PBO-controlled, parallel-group study, adult RA patients were randomized (2:1) to receive JNJ-40346527 100mg or PBO twice daily. RA patients had active disease (persistent disease activity with ≥6 swollen/6 tender joints at screening and baseline and a CRP level ≥0.8mg/dL at screening) despite MTX, SSZ, and/or HCQ therapy at the time of screening. Patients had to be on MTX, SSZ, and/or HCQ therapy for ≥6 months prior to screening, with a stable dose for minimum of 8wks prior to screening; patients were to continue stable DMARD therapy through wk12. Primary endpoint was change from baseline in DAS28 (CRP) at wk12. Efficacy analyses were based on m-ITT, defined as all randomized patients who had received ≥1 study agent administration and who had a baseline and at least one post-baseline value. Pharmacokinetics (PK) and pharmacodynamics assessments were performed.

Conclusions Despite evidence of adequate PK exposure and effective peripheral target engagement, no consistent evidence of efficacy was observed in the JNJ-40346527 group vs PBO in patients with active RA despite DMARD therapy. No statistically significant difference was observed between the groups in any of the efficacy parameters analyzed; treatment was generally well-tolerated.

Disclosure of Interest : M. Genovese Grant/research support: Janssen Research & Development, LLC, E. Hsia Employee of: Janssen Research & Development, LLC, S. Belkowski Employee of: Janssen Research & Development, LLC, C. Chien Employee of: Janssen Research & Development, LLC, T. Masterson Employee of: Janssen Research & Development, LLC, R. Thurmond Employee of: Janssen Research & Development, LLC, C. Manthey Employee of: Janssen Research & Development, LLC, D. Yan Employee of: Janssen Research & Development, LLC, T. Ge Employee of: Janssen Research & Development, LLC, A. Greenspan Employee of: Janssen Research & Development, LLC

DOI 10.1136/annrheumdis-2014-eular.2404

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