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].