A Phase 3, Randomized, Active-Controlled, Double Blind Study Comparing Upadacitinib (ABT 494) to Abatacept in Subjects with Moderately to Severely Active Rheumatoid Arthritis with Inadequate Response or Intolerance to Biologic DMARDs (bDMARDs) on Stable Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs)

Despite major progress in the treatment of RA, there still remains a large
unmet medical need, as only a small percentage of RA patients reach or maintain
a status of LDA or CR over time or need to discontinue due to safety or
tolerability issues. Novel therapies are therefore needed to complement the
available interventions to address the unmet need.

Evidence suggests that inhibition of Janus kinase (JAK)-mediated pathways is a
promising approach for the treatment of patients with this chronic disease.
AbbVie is developing a small molecule inhibitor of JAK, upadacitinib, that may
address the current needs.
Previous studies with both upadacitinib and abatacept have demonstrated robust
and statistically significant improvement in disease activity at 12 week
compared to placebo. This study differs from other upadacitinib studies as it
is the first study to evaluate the safety and efficacy of upadacitinib vs.
abatacept in subjects with inadequate response to or intolerance to bDMARD
treatment.

Main objective:
1. To compare the safety and efficacy of upadacitinib 15 mg once daily (QD)
versus abatacept intravenous (IV) for the treatment of signs and symptoms of
rheumatoid arthritis (RA) in bDMARD-inadequate response (bDMARD-IR) or
bDMARD-intolerant subjects with moderately to severely active RA.

2. To evaluate the long-term safety, tolerability, and efficacy of upadacitinib
15 mg QD in subjects with RA.

Secondary objectives:
1. Change from baseline in DAS28 (CRP) at Week 12 (superiority);

2. Proportion of subjects achieving Clinical Remission (CR) at Week 12
(superiority)

A 24-week randomized, double-blind, parallel-group, active-controlled treatment
period followed by an open label long-term extension period

Subjects who meet eligibility criteria will be randomized in a 1:1 ratio to one
of two treatment groups:
• Group 1: upadacitinib tablet QD, (Period 1)
• Group 2: Abatacept IV at Day 1, Weeks 2, 4, 8, 12, 16 and 20 (Period 1)

Subjects who complete the Week 24 visit (end of Period 1) will enter the
open-label long term extension portion of the study, Period 2 (192 weeks).
Subjects who are assigned to upadacitinib treatment group in Period 1 will
continue to receive upadacitinib QD per original randomization assignment.
Subjects who are assigned to abatacept IV in Period 1 will be switched to
receive upadacitinib 15 mg QD.

There will be higher burden for subjects participating in this trial compared
to their standard of care. Subject will be visiting the hospital more frequent
in period 1. Subjects will take daily tablets (placebo or upadacitinib) and
receive an IV infusion of abatacept or placebo. During these visits study
procedures will be performed among which blood sampling and questionnaires.
Subject will also be tested for TB, significant heart conditions, pregnancy,
HCV/HBV and HIV. Subject will also complete a daily diary.

Subjects will either receive upadacitinib or abatacept during the study. The
most frequently reported AEs (>= 5%) in the upadacitinib treated subjects were
urinary tract infection, headache, upper respiratory tract infection, and
nausea. Safety monitoring will be done during the study.

Taken together, the safety and efficacy data from the Phase 2 program show a
favorable benefit:risk profile for upadacitinib that supports further
development of upadacitinib in Phase 3 in subjects with RA.