A Study to Compare Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) With an Inadequate Response or Intolerance to Biologic DMARDs (SELECT-BEYOND)

AbbVie

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo; Drug: Upadacitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02706847

M13-542

2015-003335-35 (EudraCT Number)

Details and patient eligibility

About

The study objective of Period 1 (Day 1 to Week 24) is to compare the safety and efficacy of upadacitinib 30 mg once daily (QD) and 15 mg QD versus placebo for the treatment of signs and symptoms of participants with moderately to severely active rheumatoid arthritis (RA) who are on a stable dose of csDMARDs and had an inadequate response to or intolerance to at least 1 bDMARD.

The study objective of Period 2 (Week 24 to Week 260) is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 15 mg QD and 30 mg QD in participants with RA who completed Period 1.

Full description

This study includes a 35-day screening period; a 24-week randomized, double-blind, parallel-group, placebo controlled treatment period (Period 1); a 236-week blinded long-term extension period (Period 2); and a 30-day follow-up period (call or visit).

Period 1 consists of a 12-week double-blind, placebo-controlled treatment phase plus a 12-week double-blind phase where all participants were to receive upadacitinib; at Week 12 participants assigned to placebo will be switched to upadacitinib according to their randomization assignment.

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

• Group 1: Upadacitinib 30 mg QD (Day 1 to Week 12) → upadacitinib 30 mg QD (Week 12 and thereafter)
• Group 2: Upadacitinib 15 mg QD (Day 1 to Week 12) → upadacitinib 15 mg QD (Week 12 and thereafter)
• Group 3: Placebo (Day 1 to Week 12) → upadacitinib 30 mg QD (Week 12 and thereafter)
• Group 4: Placebo (Day 1 to Week 12) → upadacitinib 15 mg QD (Week 12 and thereafter)

Participants will continue stable dose of csDMARD therapy for the first 24 weeks of the study.

Participants who complete the Week 24 visit (end of Period 1) will enter the blinded long-term extension portion of the study, Period 2 and continue to receive the same dose of upadacitinib per original randomization assignment in a blinded manner. Starting at Week 24, at least 20% improvement in both swollen joint count (SJC) and tender joint count (TJC) compared to Baseline is required to remain on study drug. Starting at Week 24, initiation of or change in corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or adding or increasing doses in up to 2 csDMARDs (concomitant use of up to 2 csDMARDs except the combination of methotrexate and leflunomide) is allowed as per local label.

With the implementation of Protocol Amendment 4, all participants in the extension period will receive open-label upadacitinib 15 mg QD, including those currently on upadacitinib 30 mg QD.

Enrollment: 499 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of rheumatoid arthritis (RA) for≥ 3 months.
• Treated for ≥ 3 months with ≥ 1 bDMARD therapy, but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration prior to the first dose of study drug.
• Participant has been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide.
• Meets both of the following criteria:
• ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
• hsCRP ≥ 3mg/L at Screening Visit.

Exclusion criteria

• Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
• 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 including ankylosing spondylitis and non-radiographic axial spondyloarthritis, 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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499 participants in 4 patient groups, including a placebo group

Upadacitinib 15 mg

Experimental group

Description:

Period 1: Participants receive upadacitinib 15 mg once daily for 24 weeks. Period 2: Participants will continue on upadacitinib 15 mg once daily from Week 24 to Week 260.

Treatment:

Drug: Upadacitinib

Upadacitinib 30 mg

Experimental group

Description:

Period 1: Participants receive upadacitinib 30 mg once daily for 24 weeks. Period 2: Participants continue on upadacitinib 30 mg once daily until implementation of Protocol Amendment 4, then participants begin to receive upadacitinib 15 mg once daily up to Week 260.

Treatment:

Drug: Upadacitinib

Placebo / Upadacitnib 15 mg

Placebo Comparator group

Description:

Period 1: Participants receive placebo once daily for 12 weeks followed by upadacitinib 15 mg once daily for 12 weeks. Period 2: Participants will continue on upadacitinib 15 mg once daily from Week 24 to Week 260.

Treatment:

Drug: Placebo

Drug: Upadacitinib

Placebo / Upadacitnib 30 mg

Placebo Comparator group

Description:

Period 1: Participants receive placebo once daily for 12 weeks followed by upadacitinib 30 mg once daily for 12 weeks. Period 2: Participants continue on upadacitinib 30 mg once daily until implementation of Protocol Amendment 4, then participants begin to receive upadacitinib 15 mg once daily up to Week 260.

Treatment:

Drug: Placebo

Drug: Upadacitinib