A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Participants With Psoriatic Arthritis Who Have an Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (DMARD) (SELECT - PsA 1)

AbbVie

Status and phase: Active, not recruiting; Phase 3

Conditions: Psoriatic Arthritis

Treatments: Drug: Adalimumab; Drug: Placebo to Adalimumab; Drug: Placebo to Upadacitinib; Drug: Upadacitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03104400

M15-572

2016-004130-24 (EudraCT Number)

Details and patient eligibility

About

This study includes two periods. The main objective of Period 1 is to compare the efficacy of upadacitinib 15 mg once daily (QD) and 30 mg QD versus placebo and versus adalimumab (Humira®) in participants with moderately to severely active psoriatic arthritis (PsA) who have had an inadequate response to non-biologic DMARDs (DMARD-IR). Period 1 is also designed to compare the efficacy of upadacitinib 15 mg and 30 mg QD versus placebo for the prevention of structural progression.

The objective of Period 2 is to evaluate the long-term safety, tolerability and efficacy of upadacitinib 15 mg and 30 mg QD in participants who have completed Period 1.

Full description

The study includes a 35-day screening period, a 56-week blinded period (Period 1), a long-term extension period of up to a total treatment duration of approximately 5 years (Period 2), a 30-day follow-up call or visit, and a 70-day follow-up call.

Period 1 includes 24 weeks of randomized, double-blind, placebo-controlled and active comparator-controlled treatment followed by 32 weeks of active comparator-controlled upadacitinib; at Week 24 participants assigned to placebo will be switched to upadacitinib according to their randomization assignment.

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

Group 1: Upadacitinib 15 mg QD Group 2: Upadacitinib 30 mg QD Group 3: Adalimumab 40 mg every other week (EOW) Group 4: Placebo followed by upadacitinib 15 mg QD Group 5: Placebo followed by upadacitinib 30 mg QD

Randomization will be stratified by extent of psoriasis (≥ 3% body surface area [BSA] or < 3% BSA), current use of at least 1 non-biologic DMARD, presence of dactylitis, and presence of enthesitis, except for participants from China and Japan, where randomization for each country will be stratified by extent of psoriasis (≥ 3% BSA or < 3% BSA) only.

Participants who complete the Week 56 visit (end of Period 1) will enter the long-term extension portion of the study, Period 2 (total treatment up to approximately 5 years), and continue study treatment as assigned in Period 1 in a blinded manner until the last subject completes the last visit of Period 1 (Week 56), when study drug assignment in both periods will be unblinded and participants will be dispensed study drug in an open-label fashion until the completion of Period 2.

At Week 16, rescue therapy will be offered to participants classified as non-responders (defined as not achieving at least 20% improvement in tender joint count (TJC) and / or swollen joint count (SJC) at both Week 12 and Week 16). Starting at Week 36, participants who fail to demonstrate at least 20% improvement in either or both TJC and SJC compared to Baseline at 2 consecutive visits will be discontinued from study drug treatment. Additionally, in participants continuing on study drug, starting at the Week 36 visit, initiation of or change in background PsA medication(s) is allowed as per local label.

Enrollment: 1,705 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Clinical diagnosis of PsA with symptom onset at least 6 months prior to the Screening Visit and fulfillment of the Classification Criteria for PsA (CASPAR) criteria.

• Participant has active disease at Baseline defined as >= 3 tender joints (based on 68 joint counts) and >= 3 swollen joints (based on 66 joint counts) at Screening and Baseline Visits.

• Presence of either at Screening:

  1. >= 1 erosion on x-ray as determined by central imaging review or;
  2. high-sensitivity C-reactive protein (hs-CRP) > laboratory defined upper limit of normal (ULN).

• Diagnosis of active plaque psoriasis or documented history of plaque psoriasis.

• Participant has had an inadequate response (lack of efficacy after a minimum 12 week duration of therapy) to previous or current treatment with at least 1 non-biologic DMARD at maximally tolerated dose (methotrexate (MTX), sulfasalazine (SSZ), leflunomide (LEF), cyclosporine, apremilast, bucillamin or iguratimod), or participant has an intolerance to or contraindication for DMARDs as defined by the investigator.

• Participant who is on current treatment with concomitant non-biologic DMARDs at study entry must be on <= 2 non-biologic DMARDs (except the combination of MTX and leflunomide). The following non-biologic DMARDs are allowed: MTX, sulfasalazine, leflunomide, apremilast, hydroxychloroquine (HCQ) , bucillamine or iguratimod, and have been ongoing for >= 12 weeks and at stable dose for >= 4 weeks prior to the Baseline Visit. No other DMARDs are permitted during the study.

  i. Participants who need to discontinue DMARDs prior to the Baseline Visit to comply with this inclusion criterion must follow the procedure specified below or at least five times the mean terminal elimination half-life of a drug:

  1. >= 8 weeks for LEF if no elimination procedure was followed, or adhere to an elimination procedure (i.e., 11 days with cholestyramine, or 30 days washout with activated charcoal or as per local label);

  2. >= 4 weeks for all others.

     Exclusion Criteria:

• Prior exposure to any Janus Kinase (JAK) inhibitor (including but not limited to ruxolitinib, tofacitinib, baricitinib, and filgotinib).

• Current treatment with > 2 non-biologic DMARDs; or use of DMARDs other than methotrexate, sulfasalazine, leflunomide, apremilast, hydroxychloroquine, bucillamine, or iguratimod; or use of methotrexate in combination with leflunomide.

• History of fibromyalgia, any arthritis with onset prior to age 17 years, or current diagnosis of inflammatory joint disease other than PsA (including, but not limited to rheumatoid arthritis, gout, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, systemic lupus erythematosus). Prior history of reactive arthritis or axial spondyloarthritis including ankylosing spondylitis and nonradiographic axial spondyloarthritis is permitted if documentation of change in diagnosis to PsA or additional diagnosis of PsA is made. Prior history of fibromyalgia is permitted if documentation of change in diagnosis to PsA or documentation that the diagnosis of fibromyalgia was made incorrectly.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,705 participants in 5 patient groups, including a placebo group

Upadacitinib 15 mg

Experimental group

Description:

Period 1: Participants receive upadacitinib 15 mg orally once a day (QD) and matching placebo to adalimumab by subcutaneous injection every other week (EOW) for 56 weeks. Period 2: Participants will continue to receive upadacitinib 15 mg once daily.

Treatment:

Drug: Upadacitinib

Drug: Placebo to Adalimumab

Upadacitinib 30 mg

Experimental group

Description:

Period 1: Participants receive upadacitinib 30 mg orally once a day and matching placebo to adalimumab by subcutaneous injection every other week for 56 weeks. Period 2: Participants will continue to receive upadacitinib 30 mg once daily.

Treatment:

Drug: Upadacitinib

Drug: Placebo to Adalimumab

Adalimumab

Active Comparator group

Description:

Period 1: Participants receive adalimumab 40 mg by subcutaneous injection every other week and matching placebo to upadacitinib orally QD for 56 weeks. Period 2: Participants continue to receive adalimumab 40 mg every other week.

Treatment:

Drug: Placebo to Upadacitinib

Drug: Adalimumab

Placebo / Upadacitinib 15 mg

Placebo Comparator group

Description:

Period 1: Participants receive matching placebo to upadacitinib orally once a day for 24 weeks then upadacitinib 15 mg once daily for 32 weeks, and matching placebo to adalimumab by subcutaneous injection EOW for the entire 56 weeks. Period 2: Participants will continue to receive upadacitinib 15 mg once daily.

Treatment:

Drug: Upadacitinib

Drug: Placebo to Upadacitinib

Drug: Placebo to Adalimumab

Placebo / Upadacitinib 30 mg

Placebo Comparator group

Description:

Period 1: Participants receive matching placebo to upadacitinib orally once a day for 24 weeks then upadacitinib 30 mg once daily for 32 weeks, and matching placebo to adalimumab by subcutaneous injection EOW for the entire 56 weeks. Period 2: Participants will continue to receive upadacitinib 30 mg once daily.

Treatment:

Drug: Upadacitinib

Drug: Placebo to Upadacitinib

Drug: Placebo to Adalimumab