Study Design and Population
The protocol and informed consent for each of the studies were approved by the local institutional review boards. All subjects provided written informed consent before study participation. All studies were conducted according to the principles of the Declaration of Helsinki and the Good Clinical Practice Guidelines of the International Conference of Harmonisation. The study design, patient eligibility, dose administration statistical analyses, and study outcome details for the studies included in this report have been previously published (FINCH 1: NCT02889796, FINCH 2: NCT02873936, FINCH 3: NCT02886728, DARWIN 1: NCT01888874, DARWIN 2: NCT01894516) [9],[10],[16],[17],[18].
Brief summaries of the study design for each study are as follows. FINCH 1, FINCH 2, and FINCH 3 were the three Phase 3 studies included in this analysis. FINCH 1 was a randomized, double-blind, placebo- and active-controlled study in adults with moderately to severely active RA who had an inadequate response (IR) to methotrexate (MTX; MTX-IR). 1759 subjects were randomized in a 3:3:2:3 ratio to filgotinib 200 mg, filgotinib 100 mg, active comparator (adalimumab), or placebo to match (PTM) administered for up to 52 weeks, all in the context of a weekly stable dose of MTX. FINCH 2 was a randomized, double-blind, placebo-controlled study in adults who had moderately to severely active RA despite conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy (i.e., MTX, hydroxychloroquine, sulfasalazine, leflunomide) and had an inadequate response or are intolerant to at least one biologic disease-modifying antirheumatic drug (bDMARD). 449 subjects were randomized in a 1:1:1 ratio to filgotinib 200 mg, filgotinib 100 mg, or PTM administered for up to 24 weeks, all in the context of a stable dose of permitted csDMARD(s). FINCH 3 was a randomized, double-blind, placebo- and active-controlled study in adult male and female subjects with moderately to severely active RA who were naïve to MTX therapy. 1252 subjects were randomized in a 2:1:1:2 ratio to filgotinib 200 mg with MTX, filgotinib 100 mg with MTX, filgotinib 200 mg alone, or MTX alone for up to 52 weeks [9],[10],[16].
DARWIN 1 and DARWIN 2 were the two Phase 2 studies included in this analysis. DARWIN 1, a multicenter, 24-week double-blind, placebo-controlled, filgotinib add-on Phase 2b dose-finding study, was performed in subjects with moderately to severely active RA who had an inadequate response to MTX alone. A total of 594 subjects were randomized and treated: 86 subjects started in the placebo group and 508 subjects started in 1 of 6 filgotinib dose regimens: 50 mg once daily (82 subjects), 100 mg once daily (85 subjects), 200 mg once daily (86 subjects), 25 mg twice daily (86 subjects), 50 mg twice daily (85 subjects), and 100 mg twice daily (84 subjects) for 24 weeks. DARWIN 2, a multicenter, 24-week double-blind, placebo-controlled, filgotinib monotherapy Phase 2b dose-finding study, was performed in subjects with moderately to severely active RA who had an inadequate response to MTX alone. A total of 283 subjects were randomized and treated: 72 subjects started in the placebo group and 211 subjects started in 1 of 3 filgotinib monotherapy groups (72 subjects, 70 subjects, and 69 subjects were randomized to 50 mg once daily, 100 mg once daily, and 200 mg once daily, respectively, for 24 weeks) [17],[18].