A Study Comparing Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on a Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response to csDMARDs Alone (SELECT-NEXT)

AbbVie

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo; Drug: Upadacitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02675426

M13-549

2015-003332-13 (EudraCT Number)

Details and patient eligibility

About

The primary objectives of this study are to compare the efficacy, safety, and tolerability of upadacitinib 30 mg once daily (QD) and 15 mg QD versus placebo for the treatment of signs and symptoms of adults with moderately to severely active rheumatoid arthritis who were on a stable dose of csDMARDs and had an inadequate response to csDMARDs.

Full description

This Phase 3 multicenter study includes two periods. Period 1 is a 12-week, randomized, double-blind, parallel-group, placebo-controlled period designed to compare the safety and efficacy of upadacitinib 30 mg once daily and upadacitinib 15 mg once daily versus placebo for the treatment of signs and symptoms of adults with moderately to severely active rheumatoid arthritis (RA) who were on a stable dose of csDMARDs and had an inadequate response to csDMARDs.

Period 2 is a 248-week blinded long-term extension period to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 30 mg once daily and upadacitinib 15 mg once daily in participants who completed Period 1.

Participants were to be randomized in a 2:2:1:1 ratio using interactive response technology (IRT) to receive double-blind study drug in one of the following treatment groups:

• Group 1: Upadacitinib 30 mg QD in Period 1 → Upadacitinib 30 mg QD in Period 2
• Group 2: Upadacitinib 15 mg QD in Period 1 → Upadacitinib 15 mg QD in Period 2
• Group 3: Placebo in Period 1 → Upadacitinib 30 mg QD in Period 2
• Group 4: Placebo in Period 1 → Upadacitinib 15 mg QD in Period 2

Randomization was stratified by prior exposure to biological disease-modifying anti-rheumatic drug (bDMARD) (yes/no) and geographic region.

Following Protocol Amendment 6.0 approval in December 2019, all participants still on study received open-label upadacitinib 15 mg QD, including those on upadacitinib 30 mg QD, with the earliest switch occurring at the Week 168 visit.

Enrollment: 661 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult male or female, at least 18 years old.
• Diagnosis of rheumatoid arthritis (RA) for greater than or equal to 3 months.
• Subjects have been receiving conventional synthetic DMARD (csDMARD) therapy for greater than or equal to 3 months and on a stable dose for greater than or equal to 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide.
• Meets the following minimum disease activity criteria: greater than or equal to 6 swollen joints (based on 66 joint counts) and greater than or equal to 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
• Subjects with prior exposure to at most one biologic DMARD (bDMARD) may be enrolled (up to 20% of study population) if they have documented evidence of intolerance to bDMARDs or limited exposure (less than 3 months) and have satisfied required washout periods.

Exclusion criteria

• Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
• History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.
• Subjects who are considered inadequate responders to bDMARD therapy as determined by the Investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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661 participants in 4 patient groups

Upadacitinib 15 mg

Experimental group

Description:

Period 1: Participants receive upadacitinib 15 mg once daily for 12 weeks. Period 2: Participants continue to receive upadacitinib 15 mg once daily for an additional 248 weeks.

Treatment:

Drug: Upadacitinib

Upadacitinib 30 mg

Experimental group

Description:

Period 1: Participants receive upadacitinib 30 mg once daily for 12 weeks. Period 2: Participants continue to receive upadacitinib 30 mg once daily for an additional 248 weeks or until implementation of Protocol Amendment 6 at which time participants switch to receive upadacitinib 15 mg once daily.

Treatment:

Drug: Upadacitinib

Placebo / Upadacitinib 15 mg

Experimental group

Description:

Period 1: Participants receive placebo once daily for 12 weeks. Period 2: Participants receive upadacitinib 15 mg once daily for 248 weeks.

Treatment:

Drug: Placebo

Drug: Upadacitinib

Placebo / Upadacitinib 30 mg

Experimental group

Description:

Period 1: Participants receive placebo once daily for 12 weeks. Period 2: Participants receive upadacitinib 30 mg once daily for 248 weeks or until implementation of Protocol Amendment 6 at which time participants switch to receive upadacitinib 15 mg once daily.

Treatment:

Drug: Placebo

Drug: Upadacitinib