A Study to Compare Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have Not Previously Taken Methotrexate (SELECT-EARLY)

Brief Summary:
The objectives of Period 1 were the following:
1. To compare the safety and efficacy of upadacitinib 7.5 mg once daily (QD) monotherapy (for participants in Japan only), 15 mg QD monotherapy, and 30 mg QD monotherapy versus weekly methotrexate monotherapy for the treatment of signs and symptoms of RA in methotrexate-naïve adults with moderately to severely active RA;
2. To compare the efficacy of upadacitinib 15 mg QD monotherapy and upadacitinib 30 mg QD monotherapy versus weekly methotrexate monotherapy for prevention of structural progression in methotrexate-naïve adults with moderately to severely active RA.

The objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 7.5 mg QD (for participants in Japan only), 15 mg QD, and 30 mg QD in adults with RA who have completed Period 1.

Detailed Description:
This study includes 2 periods (a 48-week double-blind treatment period and a long-term extension period) and a Japan substudy. In Period 1 participants will be randomized in a 1:1:1 ratio to treatment Groups 2, 3, and 4 below, except for participants from Japan, who will be randomized in a 2:1:1:1 ratio to Groups 1, 2, 3, and 4:
- Group 1: Upadacitinib 7.5 mg once daily (QD) monotherapy (participants in Japan only)
- Group 2: Upadacitinib 15 mg QD monotherapy
- Group 3: Upadacitinib 30 mg QD monotherapy
- Group 4: Methotrexate monotherapy

Participants who complete the Week 48 visit (end of Period 1) will enter the long-term extension, Period 2 (192 weeks) and continue study treatment per assignment at the end of Period 1 in a blinded fashion.

A global analysis will be conducted for the comparisons of the primary and secondary efficacy endpoints between the upadacitinib 15 mg QD and 30 mg QD treatment groups versus the methotrexate treatment group for all participants (excluding the Japan specific upadacitinib 7.5 mg treatment group). Analyses will be conducted separately for United States (US)/Food and Drug Administration (FDA), European Union (EU)/European Medicines Agency (EMA), and Japan/Pharmaceuticals and Medical Devices Agency (PMDA) regulatory purposes, each according to a pre-specified sequence of primary and ranked secondary endpoints.

A separate Japan sub-study analysis will be conducted for the comparisons of the efficacy endpoints between the upadacitinib 7.5 mg QD, 15 mg QD, and 30 mg QD treatment groups versus the methotrexate treatment group for participants enrolled in Japan only.


Study Type: Interventional  (Clinical Trial)
Actual Enrollment: 1002 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Participants were to be randomized in a 1:1:1 ratio to treatment Groups 2, 3, and 4 below, except for participants from Japan, who were to be randomized in a 2:1:1:1 ratio to Groups 1, 2, 3, and 4:
- Group 1: Upadacitinib 7.5 mg QD monotherapy (Japan only)
- Group 2: Upadacitinib 15 mg QD monotherapy (43 countries, including Japan)
- Group 3: Upadacitinib 30 mg QD monotherapy (43 countries, including Japan)
- Group 4: MTX monotherapy (43 countries, including Japan)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) Once Daily Monotherapy to Methotrexate (MTX) Monotherapy in MTX-Naïve Subjects With Moderately to Severely Active Rheumatoid Arthritis
Actual Study Start Date: February 23, 2016
Actual Primary Completion Date: March 15, 2018
Estimated Study Completion Date: June 4, 2022

Arms:
- Active Comparator: Methotrexate
- Experimental: Upadacitinib 7.5 mg
- Experimental: Upadacitinib 15 mg
- Experimental: Upadacitinib 30 mg