Improved disease activity with fosdagrocorat (PF-04171327), a partial agonist of the glucocorticoid receptor, in patients with rheumatoid arthritis: a Phase 2 randomized study

Abstract

Aim: To assess efficacy and safety of fosdagrocorat (PF-04171327), a potential dissociated agonist of the glucocorticoid receptor, in rheumatoid arthritis (RA) patients. Methods: This multicenter, double-blind, parallel-group, active- and placebo-controlled Phase 2 study (NCT00938587) randomized 86 patients (1 : 1 : 1 : 1) to receive fosdagrocorat 10 mg, fosdagrocorat 25 mg, prednisone 5 mg or placebo, all with stable background methotrexate therapy. The primary outcome was change from baseline in Disease Activity Score of 28 joints (DAS28-4[C-reactive protein (CRP)]) after 2 weeks of treatment. Secondary outcomes included American College of Rheumatology (ACR) response rates, change from baseline in ACR core components and Health Assessment Questionnaire Disability Index. Results: At week 2, improvements from baseline in DAS28-4(CRP) with fosdagrocorat 10 and 25 mg, prednisone 5 mg and placebo were −1.69, −2.22, −1.17 and −0.96, respectively, and were statistically significantly greater for both fosdagrocorat doses versus placebo (P < 0.05) and for fosdagrocorat 25 mg versus prednisone 5 mg (P < 0.001). The effects of fosdagrocorat on secondary outcomes were generally consistent with those observed for the primary outcome. Adverse events (AEs) were reported for eight (38%), three (14%), four (19%) and 12 (55%) patients treated with fosdagrocorat 10 and 25 mg, prednisone 5 mg and placebo, respectively. Most AEs were mild in severity. Four patients discontinued treatment due to AEs (fosdagrocorat 10 mg, n = 2; placebo, n = 2). There were no serious AEs. Conclusion: Fosdagrocorat 10 and 25 mg demonstrated efficacy in improving signs and symptoms in RA patients, with manageable AEs. Additional studies are needed to assess the longer-term safety and efficacy of fosdagrocorat.