A Study Comparing Upadacitinib (ABT-494) to Placebo in Participants With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Biologic Disease Modifying Anti-Rheumatic Drug (bDMARD) (SELECT - PsA 2)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03104374 |
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Recruitment Status :
Active, not recruiting
First Posted : April 7, 2017
Results First Posted : January 25, 2022
Last Update Posted : October 6, 2022
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The study objectives of Period 1 are to compare the efficacy, safety, and tolerability of upadacitinib 15 mg once daily (QD) and 30 mg QD versus placebo for the treatment of signs and symptoms in adults with moderately to severely active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to biologic disease-modifying anti-rheumatic drug (bDMARD).
The objective of Period 2 is to evaluate the long-term safety, tolerability and efficacy of upadacitinib 15 mg QD and 30 mg QD in participants who have completed Period 1.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Psoriatic Arthritis | Drug: Upadacitinib Drug: Placebo | Phase 3 |
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 3 years (Period 2), and a 30-day follow-up call or visit.
Period 1 includes 24 weeks of randomized, double-blind, parallel-group, placebo-controlled treatment followed by an additional 32 weeks of blinded treatment where all participants were to receive 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 2:2:1:1 ratio to one of four treatment groups:
- Group 1: Upadacitinib 15 mg
- Group 2: Upadacitinib 30 mg
- Group 3: Placebo for 24 weeks followed by upadacitinib 15 mg
- Group 4: Placebo for 24 weeks followed by upadacitinib 30 mg
Participants who complete the Week 56 visit (end of Period 1) will enter the long-term extension portion of the study, Period 2, and continue study treatment as assigned in Period 1 in a blinded manner until the last participant completes the last visit of Period 1 (Week 56), when study drug assignment in both periods will be unblinded and study drug will be dispensed 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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 642 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo in Subjects With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Biologic Disease Modifying Anti-Rheumatic Drug (bDMARD) - SELECT - PsA 2 |
| Actual Study Start Date : | May 1, 2017 |
| Actual Primary Completion Date : | July 23, 2019 |
| Estimated Study Completion Date : | March 30, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Upadacitinib 15 mg
Period 1: Participants receive upadacitinib 15 mg once daily for 56 weeks. Period 2: Participants will continue to receive upadacitinib 15 mg once daily. |
Drug: Upadacitinib
Oral tablet
Other Names:
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Experimental: Upadacitinib 30 mg
Period 1: Participants receive upadacitinib 30 mg once daily for 56 weeks. Period 2: Participants will continue to receive upadacitinib 30 mg once daily. |
Drug: Upadacitinib
Oral tablet
Other Names:
|
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Placebo Comparator: Placebo then Upadacitinib 15 mg
Period 1: Participants receive placebo once daily for 24 weeks followed by upadacitinib 15 mg once daily for 32 weeks. Period 2: Participants will continue to receive upadacitinib 15 mg once daily. |
Drug: Upadacitinib
Oral tablet
Other Names:
Drug: Placebo Oral tablet |
|
Placebo Comparator: Placebo then Upadacitinib 30 mg
Period 1: Participants receive placebo once daily for 24 weeks followed by upadacitinib 30 mg once daily for 32 weeks. Period 2: Participants will continue to receive upadacitinib 30 mg once daily. |
Drug: Upadacitinib
Oral tablet
Other Names:
Drug: Placebo Oral tablet |
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Baseline and Week 12 ]
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:
- ≥ 20% improvement in 68-tender joint count;
- ≥ 20% improvement in 66-swollen joint count; and
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≥ 20% improvement in at least 3 of the 5 following parameters:
- Physician global assessment of disease activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 [ Time Frame: Baseline and Week 12 ]
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.
A negative change from Baseline in the overall score indicates improvement.
- 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 [ Time Frame: Baseline and Week 16 ]The sIGA is a 5 point scale ranging from 0 to 4, based on the investigator's assessment of the average elevation, erythema, and scaling of all psoriatic lesions at the current visit. A lower score indicates less severe psoriasis (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe).
- Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response at Week 16 [ Time Frame: Baseline and Week 16 ]
PASI is a composite score based on the percentage of the body surface area (BSA) affected by psoriasis and the intensity of erythema (reddening), induration (thickening or hardening of the skin), and desquamation (peeling of the skin) of lesions assessed at 4 anatomic sites (head, upper extremities, trunk, and lower extremities). At each location, the percentage of BSA involvement is assigned a score from 0 (no involvement) to 6 (90% to 100% involvement), and erythema, induration, and desquamation are scored on a scale from 0 (no symptoms) to 4 (very marked).
The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from Baseline in PASI score.
- Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 [ Time Frame: Baseline and Week 12 ]
The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 [ Time Frame: Baseline and Week 12 ]The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days, including physical fatigue (e.g., I feel tired), functional fatigue (e.g., trouble finishing things), emotional fatigue (e.g., frustration), and social consequences of fatigue (e.g., limits social activity). Participants respond to the questions on a scale from 0 'not at all' to 4 'very much'. The FACIT Fatigue score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue. A positive change from Baseline indicates improvement.
- Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24 [ Time Frame: Week 24 ]
A participant was classified as achieving MDA if 5 of the following 7 criteria were met:
- Tender joint count (out of 68 joints) ≤ 1
- Swollen joint count (out of 66 joints) ≤ 1
- PASI score ≤ 1 (score ranges from 0 - 72) or percent BSA involved with psoriasis ≤ 3%
- Patient's assessment of pain ≤ 1.5 (NRS from 0 to 10)
- Patient's Global Assessment of disease activity ≤ 2 (NRS from 0 to 10)
- HAQ-DI score ≤ 0.5 (index score ranges from 0 to 3)
- Leeds Enthesitis Index ≤ 1 (assesses the presence or absence of enthesitis at 3 bilateral sites, with an overall score range from 0 to 6)
- Change From Baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Score at Week 16 [ Time Frame: Baseline and Week 16 ]The SAPS is an 11-item self-assessment of psoriasis symptoms that includes questions on: pain, itching, redness, scaling, flaking, bleeding, burning, stinging, tenderness, pain due to skin cracking, and joint pain. Each item is scored from 0 to 10, with 0 being least severe and 10 being most severe. The total score is generated by summing the 11 items and ranges from 0 to 110 (worst). A negative change from Baseline in the total score indicates improvement.
- Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 [ Time Frame: Baseline and Week 12 ]
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:
- ≥ 50% improvement in 68-tender joint count;
- ≥ 50% improvement in 66-swollen joint count; and
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≥ 50% improvement in at least 3 of the 5 following parameters:
- Physician global assessment of disease activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
- Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 [ Time Frame: Baseline and Week 12 ]
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria:
- ≥ 70% improvement in 68-tender joint count;
- ≥ 70% improvement in 66-swollen joint count; and
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≥ 70% improvement in at least 3 of the 5 following parameters:
- Physician global assessment of disease activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2 [ Time Frame: Baseline and Week 2 ]
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:
- ≥ 20% improvement in 68-tender joint count;
- ≥ 20% improvement in 66-swollen joint count; and
-
≥ 20% improvement in at least 3 of the 5 following parameters:
- Physician global assessment of disease activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
- 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) or intolerance to treatment with at least 1 bDMARD.
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 (MTX), sulfasalazine (SSZ), leflunomide (LEF), apremilast, hydroxychloroquine (HCQ), bucillamine or iguratimod or use of MTX in combination with LEF at Baseline.
- 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 non-radiographic 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03104374
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| Study Director: | AbbVie Inc. | AbbVie |
Documents provided by AbbVie:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AbbVie |
| ClinicalTrials.gov Identifier: | NCT03104374 |
| Other Study ID Numbers: |
M15-554 2016-004152-30 ( EudraCT Number ) |
| First Posted: | April 7, 2017 Key Record Dates |
| Results First Posted: | January 25, 2022 |
| Last Update Posted: | October 6, 2022 |
| Last Verified: | September 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. |
| Access Criteria: | Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link. |
| URL: | https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Arthritis Psoriasis Anti-Rheumatic |
Anti-inflammatory Joint disease Musculoskeletal disease |
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Arthritis Arthritis, Psoriatic Rheumatic Diseases Joint Diseases Musculoskeletal Diseases Spondylarthropathies Spondylarthritis Spondylitis Spinal Diseases Bone Diseases |
Psoriasis Skin Diseases, Papulosquamous Skin Diseases Connective Tissue Diseases Upadacitinib Janus Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antirheumatic Agents |