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Improved disease activity with fosdagrocorat ( PF ‐04171327), a partial agonist of the glucocorticoid receptor, in patients with rheumatoid arthritis: a Phase 2 randomized study
Author(s) -
Stock Thomas,
Fleishaker Dona,
Wang Xin,
Mukherjee Arnab,
Mebus Charles
Publication year - 2017
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.13053
Subject(s) - medicine , prednisone , rheumatoid arthritis , placebo , rheumatology , adverse effect , gastroenterology , methotrexate , corticosteroid , randomized controlled trial , pathology , alternative medicine
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 ( NCT 00938587) 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 ( DAS 28‐4[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 DAS 28‐4( 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 ( AE s) 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 AE s were mild in severity. Four patients discontinued treatment due to AE s (fosdagrocorat 10 mg, n = 2; placebo, n = 2). There were no serious AE s. Conclusion Fosdagrocorat 10 and 25 mg demonstrated efficacy in improving signs and symptoms in RA patients, with manageable AE s. Additional studies are needed to assess the longer‐term safety and efficacy of fosdagrocorat.