A Study Comparing Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have an Inadequate Response to MTX (SELECT-MONOTHERAPY)

AbbVie

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Upadacitinib; Drug: Placebo Methotrexate; Drug: Placebo Upadacitinib; Drug: Methotrexate

Study type: Interventional

Funder types: Industry

Identifiers

NCT02706951

2015-003376-75 (EudraCT Number)

M15-555

Details and patient eligibility

About

The study objective of Period 1 of this study is to compare the safety and efficacy (signs and symptoms) of upadacitinib 30 mg once daily (QD) alone and upadacitinib 15 mg QD alone versus continuing MTX alone adults with moderately to severely active rheumatoid arthritis (RA) with an inadequate response to MTX.

The study objective of Period 2 is to evaluate the long term safety, tolerability, and efficacy of upadacitinib 30 mg QD and 15 mg QD in adults with RA who had completed Period 1.

Full description

The study includes a 35-day screening period; a 14-week randomized, double-blind, parallel-group, controlled treatment period (Period 1); a 246-week blinded extension period (Period 2); and a 30-day follow-up visit.

Participants who met eligibility criteria were to be randomized in a 2:2:1:1 ratio to one of four treatment groups:

• Group 1: upadacitinib 30 mg QD (Period 1) → upadacitinib 30 mg QD (Period 2)
• Group 2: upadacitinib 15 mg QD (Period 1) → upadacitinib 15 mg QD (Period 2)
• Group 3: MTX (Period 1) → upadacitinib 30 mg QD (Period 2)
• Group 4: MTX (Period 1) → upadacitinib 15 mg QD (Period 2)

Starting with implementation of Protocol Amendment 5, all participants in the extension period will receive open-label upadacitinib 15 mg QD, including those currently on upadacitinib 30 mg QD.

Enrollment: 648 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of RA for >= 3 months.
• Subjects must have been on oral or parenteral MTX therapy >= 3 months and on a stable dose for >= 4 weeks prior to first dose of study drug.
• Must have discontinued all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) (other than MTX) >= 4 weeks prior to first dose of study drug.
• Meets the following minimum disease activity criteria: >= 6 swollen joints (based on 66 joint counts) and >= 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.

Exclusion criteria

• Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
• Prior exposure to any biological disease-modifying anti-rheumatic drugs (bDMARDs).
• Current diagnosis of inflammatory joint disease other than RA. Current diagnosis of secondary Sjogren's Syndrome is permitted.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

648 participants in 4 patient groups

Upadacitinib 30 mg

Experimental group

Description:

Period 1: Participants receive upadacitnib 30 mg once daily and placebo to methotrexate once weekly for 14 weeks. Period 2: Participants receive upadacitinib 30 mg once daily until implementation of Protocol Amendment 5 when participants begin to receive upadacitinib 15 mg once daily up to Week 260.

Treatment:

Drug: Placebo Methotrexate

Drug: Upadacitinib

Upadacitinib 15 mg

Experimental group

Description:

Period 1: Participants receive upadacitnib 15 mg once daily and placebo to methotrexate once weekly for 14 weeks. Period 2: Participants receive upadacitinib 15 mg once daily up to Week 260.

Treatment:

Drug: Placebo Methotrexate

Drug: Upadacitinib

Methotrexate / Upadacitinib 30 mg

Experimental group

Description:

Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib once daily for 14 weeks. Period 2: Participants receive upadacitinib 30 mg once daily until implementation of Protocol Amendment 5 when participants begin to receive upadacitinib 15 mg once daily up to Week 260.

Treatment:

Drug: Placebo Methotrexate

Drug: Placebo Upadacitinib

Drug: Upadacitinib

Drug: Methotrexate

Methotrexate / Upadacitinib 15 mg

Experimental group

Description:

Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib for 14 weeks. Period 2: Participants receive upadacitinib 15 mg once daily up to Week 260.

Treatment:

Drug: Placebo Methotrexate

Drug: Placebo Upadacitinib

Drug: Upadacitinib

Drug: Methotrexate