Phase 3
N=1,705
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)
Psoriatic Arthritis
Bottom Line
View on ClinicalTrials.gov: NCT03104400 ↗Enrolled (actual)
1,705
Serious AEs
12.7%
Results posted
Jan 2022
Primary outcome: Primary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 — 36.2; 65.0; 70.6; 78.5 percentage of participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Adalimumab (Drug); Upadacitinib (Drug); Placebo to Upadacitinib (Drug); Placebo to Adalimumab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AbbVie
- Primary completion
- Sep 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 |
36.2; 65.0; 70.6; 78.5 | <0.0001 sig |
| SECONDARY Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 |
-0.14; -0.34; -0.42; -0.47 | <0.0001 sig |
| SECONDARY Percentage of Participants Achieving a Static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at Least a 2-point Improvement From Baseline (sIGA 0/1) at Week 16 |
10.9; 38.5; 41.9; 54.0 | <0.0001 sig |
| SECONDARY Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response at Week 16 |
21.3; 53.1; 62.6; 62.4 | <0.0001 sig |
| SECONDARY Change From Baseline in Modified PsA Total Sharp/Van Der Heijde Score (mTSS) at Week 24 |
0.25; 0.01; -0.04; 0.03 | 0.0002 sig |
| SECONDARY Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24 |
12.3; 33.3; 36.6; 45.4 | <0.0001 sig |
| SECONDARY Percentage of Participants With Resolution of Enthesitis at Week 24 |
32.4; 47.2; 53.7; 57.7 | <0.0001 sig |
| SECONDARY Percentage of Participants With an ACR20 Response at Week 12 - Non-inferiority Versus Adalimumab |
36.2; 65.0; 70.6; 78.5 | <0.0001 sig |
| SECONDARY Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 |
3.19; 6.82; 7.86; 8.90 | <0.0001 sig |
| SECONDARY Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 |
2.8; 5.7; 6.3; 7.1 | <0.0001 sig |
| SECONDARY Percentage of Participants With an ACR20 Response at Week 12 - Superiority Versus Adalimumab |
36.2; 65.0; 70.6; 78.5 | 0.0815 |
| SECONDARY Percentage of Participants With Resolution of Dactylitis at Week 24 |
39.7; 74.0; 76.5; 79.5 | <0.0001 sig |
| SECONDARY Change From Baseline in Patient's Assessment of Pain - Superiority Versus Adalimumab |
-0.9; -2.3; -2.3; -2.7 | 0.8970 |
| SECONDARY Change From Baseline in HAQ-DI - Superiority Versus Adalimumab |
-0.14; -0.34; -0.42; -0.47 | 0.0162 sig |
| SECONDARY Change From Baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Questionnaire at Week 16 |
-8.2; -22.7; -25.3; -28.1 | <0.0001 sig |
| SECONDARY Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 |
13.2; 37.5; 37.5; 51.8 | <0.0001 sig |
| SECONDARY Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 |
2.4; 13.8; 15.6; 25.3 | <0.0001 sig |
| SECONDARY Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2 |
12.1; 30.3; 28.2; 38.3 | <0.0001 sig |
Summary
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.
Eligibility 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 erosion on x-ray as determined by central imaging review or;
- 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 = 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:
- >= 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);
- >= 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.
Data sourced from ClinicalTrials.gov (NCT03104400). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.