A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Background of Methotrexate (MTX) and Who Have an Inadequate Response to MTX (MTX-IR)
A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Background of Methotrexate (MTX) and Who Have an Inadequate Response to MTX (MTX-IR)
The purpose of this study was to assess efficacy, including inhibition of radiographic progression, and safety with upadacitinib versus placebo and versus an active comparator, adalimumab, in adults with with moderately to severely active rheumatoid arthritis (RA) who are on a stable background of methotrexate (MTX and who have an inadequate response to MTX.
This study consists of a 48-week double-blind treatment period (Period 1) and a long-term extension period (Period 2).
Period 1 is a 48-week randomized, double-blind, parallel-group, placebo-controlled and active comparator-controlled period designed to compare the safety and efficacy of upadacitinib versus placebo, and versus adalimumab. Participants will be randomized in a 2:2:1 ratio to one of three treatment groups:
Participants randomized to placebo who do not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib treatment. At Week 26, all participants still receiving placebo will be switched to blinded upadacitinib treatment regardless of clinical response.
Participants randomized to adalimumab who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib. Participants still receiving adalimumab at Week 26 who do not achieve low disease activity (LDA) according to Clinical Disease Activity Index (CDAI; LDA is defined as CDAI ≤ 10) will be switched to blinded upadacitinib treatment to Week 48.
Participants randomized to upadacitinib who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded adalimumab; participants still receiving upadacitinib at Week 26 who do not achieve LDA (CDAI ≤ 10) will be switched to blinded adalimumab treatment to Week 48.
Participants who complete the Week 48 visit (end of Period 1) will enter the long-term extension phase of the study (Period 2), for up to 5 years. Participants will continue study treatment as assigned at the end of Period 1. Starting at the Week 48 and thereafter, at least 20% improvement in both TJC and SJC compared to Baseline is required to remain on study drug. Anyone who does not fulfill this criterion at 2 consecutive visits (starting at Week 48) will be discontinued.
Inclusion Criteria:
Exclusion Criteria:
Tucson, Arizona 85719-1478, United States
Summerville, South Carolina 29486-7887, United States
Capital Federal, Buenos Aires 1046, Argentina
Rosario, Santa FE, 2000, Argentina
Banja Luka, Republika Srpska 78000, Bosnia and Herzegovina
Banja Luka, Republika Srpska 78000, Bosnia and Herzegovina
São Paulo, São Paulo 04266-010, Brazil
Providencia-santiago, 7510186, Chile
Bogota, Cundinamarca 110221, Colombia
Bogota DC, Colombia
Miskolc, Borsod-Abauj Zemplen county 3529, Hungary
Budapest III, Pest County 1036, Hungary
Wroclaw, Lower Silesian Voivodeship 51-685, Poland
Warsaw, Masovian Voivodeship 02-507, Poland
Korolev, Moscow 141060, Russia
Pieštany, 921 01, Slovakia
Stará Lubovna, 06401, Slovakia
Seongdong-gu, Seoul Teugbyeolsi 04763, South Korea
Taipei City, Taipei 10002, Taiwan
Istanbul, 34147, Turkey (Türkiye)
Kiev, Kyiv Oblast 04070, Ukraine
Vinnytsia, Vinnytsia Oblast 21018, Ukraine
Zaporizhia, 69600, Ukraine