A Study to Compare Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis (RA) Who Are on a Stable Dose of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) and Have an Inadequate Response to csDMARDs (SELECTSUNRISE)

AbbVie

Status and phase: Completed; Phase 3; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Upadacitinib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02720523

M14-663

Details and patient eligibility

About

This is a randomized, double-blind study comparing ABT-494 to placebo in Japanese participants with moderately to severely active rheumatoid arthritis who are on a stable dose of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and have an inadequate response.

Following marketing approval of upadacitinib for rheumatoid arthritis in Japan, this study will become a post-marketing clinical study and include a long-term extension period.

Full description

This study consisted of a 35-day screening period; a 12-week randomized, double-blind, parallel-group, placebo-controlled treatment period (Period 1); a 248-week blinded long-term extension period (Period 2); and a 30-day follow-up period (call or visit).

Participants who met eligibility criteria were randomized in a 3:3:3:1:1:1 ratio to one of six treatment groups:

• Group 1: Upadacitinib 7.5 mg QD (Period 1) → upadacitinib 7.5 mg QD (Period 2)
• Group 2: Upadacitinib 15 mg QD (Period 1) → upadacitinib 15 mg QD (Period 2)
• Group 3: Upadacitinib 30 mg QD (Period 1) → upadacitinib 30 mg QD (Period 2)
• Group 4: Placebo (Period 1) → upadacitinib 7.5 mg QD (Period 2)
• Group 5: Placebo (Period 1) → upadacitinib 15 mg QD (Period 2)
• Group 6: Placebo (Period 1) → upadacitinib 30 mg QD (Period 2)

Enrollment: 197 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of rheumatoid arthritis (RA) for >= 3 months who also fulfill the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA.

• Subjects have been receiving conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy >= 3 months and on a stable dose for >= 4 weeks prior to the first dose of study drug.

• Subject has >= 6 swollen joints (based on 66 joint counts) and >= 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.

• Subjects with prior exposure to at most one biological disease-modifying anti-rheumatic drug (bDMARD) may be enrolled (up to 20% of total number of subjects) after the required washout period. Specifically, prior to enrollment:

  1. Subjects with limited exposure to bDMARD (< 3 months) OR
  2. Subjects who are responding to bDMARD therapy but had to discontinue due to intolerability (regardless of treatment duration).

Exclusion criteria

• Prior exposure to any Janus kinase (JAK) inhibitor
• Subjects who are considered inadequate responders (lack of efficacy) to bDMARD therapy, after minimum 3 months treatment, as determined by the Investigator.
• History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis [SpA] including ankylosing spondylitis and non-radiographic axial SpA, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms]). Current diagnosis of secondary Sjogren's Syndrome is permitted.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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197 participants in 6 patient groups

Placebo / Upadacitinib 7.5 mg

Experimental group

Description:

Period 1: Participants will receive placebo once daily for 12 weeks. Period 2: Participants will receive Upadacitinib 7.5 mg once daily for 248 weeks.

Treatment:

Drug: Placebo

Drug: Upadacitinib

Placebo / Upadacitinib 15 mg

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: Upadacitinib

Placebo / Upadacitinib 30 mg

Experimental group

Description:

Period 1: Participants will receive placebo once daily for 12 weeks. Period 2: Participants will receive upadacitinib 30 mg once daily until regulatory approval of RA indication in Japan at which point they will switch to receive upadacitinib 15 mg once daily. Participants will receive upadacitinib for 248 weeks.

Treatment:

Drug: Placebo

Drug: Upadacitinib

Upadacitinib 7.5 mg / Upadacitinib 7.5 mg

Experimental group

Description:

Period 1: Participants will receive upadacitinib 7.5 mg once daily for 12 weeks. Period 2: Participants will receive upadacitinib 7.5 mg once daily for 248 weeks.

Treatment:

Drug: Upadacitinib

Upadacitinib 15 mg / Upadacitinib 15 mg

Experimental group

Description:

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

Treatment:

Drug: Upadacitinib

Upadacitinib 30 mg / Upadacitinib 30 mg

Experimental group

Description:

Period 1: Participants will receive upadacitinib 30 mg once daily for 12 weeks. Period 2: Participants will receive upadacitinib 30 mg once daily until regulatory approval of RA indication in Japan at which point they will switch to receive upadacitinib 15 mg once daily. Participants will receive upadacitinib for 248 weeks.

Treatment:

Drug: Upadacitinib