Oral administration of GLPG0259, an inhibitor of MAPKAPK5, a new target for the treatment of rheumatoid arthritis: a phase II, randomised, double-blind, placebo-controlled, multicentre trial
- René Westhovens1,
- Filip De Keyser2,
- Dmytro Rekalov3,
- Evgeny L Nasonov4,
- Johan Beetens5,
- Annegret Van der Aa5,
- Piet Wigerinck5,
- Florence Namour6,
- Frédéric Vanhoutte5,
- Patrick Durez7
- 1Department of Rheumatology, University Hospital KU Leuven, Leuven, Belgium
- 2Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
- 3Department of Rheumatology, Zaporizhzhia Regional Hospital, Zaporozhe, Ukraine
- 4Department of Rheumatology, Institute of Rheumatology, Moscow, Russia
- 5Clinical Development Department, Galápagos NV, Mechelen, Belgium
- 6Clinical Development Department, Galápagos SASU, Romainville, France
- 7Department of Rheumatology, Université Catholique de Louvain, Brussels, Belgium
- Correspondence to Dr Frédéric Vanhoutte, Galápagos NV, Gen De Wittelaan L11 A3, Mechelen 2800, Belgium;
- Accepted 20 October 2012
- Published Online First 17 November 2012
Background Mitogen-activated protein (MAP) kinases are key regulators of cytokine production, and are therefore potential targets for treatment of rheumatoid arthritis (RA).
Objective This two-part phase II study investigated the efficacy and safety of a once-daily 50 mg GLPG0259 (an inhibitor of MAP kinase-activated protein kinase 5) dose vs placebo (part A). An interim analysis after part A would determine whether the dose-finding part (part B) would be performed.
Methods In part A, eligible methotrexate (MTX)-refractory patients with RA were randomised to receive either a once-daily 50 mg dose of GLPG0259 or placebo, in addition to a stable dose of MTX, for 12 weeks. The primary efficacy end point was the percentage of patients achieving an American College of Rheumatology 20% improvement (ACR20) response after 12 weeks.
Results The interim analysis showed no difference between the percentage of subjects achieving the primary efficacy variable of ACR20 or the secondary efficacy variables (ACR50, ACR70 and Disease Activity Score 28) at week 12 in the GLPG0259-treated (n=19) and placebo-treated (n=11) groups. Owing to lack of efficacy, the study was terminated, and part B was not initiated.
Conclusions This innovative study design quickly provided conclusive results on the lack of efficacy of GLPG0259 in patients with RA.