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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 (SELECT - PsA 1)

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ClinicalTrials.gov Identifier: NCT03104400
Recruitment Status : Recruiting
First Posted : April 7, 2017
Last Update Posted : December 3, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:
This is a Phase 3 multicenter study that includes two periods. Period 1 is designed to compare the safety, tolerability, and efficacy of ABT-494 Dose A once daily (QD) and Dose B QD versus placebo and versus adalimumab every other week (eow) in participants with moderately to severely active Psoriatic Arthritis (PsA) and have an inadequate response to non-biologic DMARDs (DMARD-IR). Period 1 is also designed to compare the efficacy of ABT-494 Dose A QD and Dose B QD versus placebo for the prevention of structural progression. Period 2 evaluates the safety, tolerability and efficacy of ABT-494 Dose A QD and Dose B QD in participants with PsA who have completed Period 1.

Condition or disease Intervention/treatment Phase
Psoriatic Arthritis Drug: Adalimumab Drug: ABT-494 Drug: Placebo for ABT-494 Drug: Placebo for Adalimumab Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1640 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 and to Adalimumab in Subjects With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (DMARD) - SELECT - PsA 1
Actual Study Start Date : April 27, 2017
Estimated Primary Completion Date : October 23, 2019
Estimated Study Completion Date : September 6, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Adalimumab

Arm Intervention/treatment
Placebo Comparator: Placebo followed by ABT-494 Dose B
It is administered once daily.
Drug: ABT-494
Oral tablet
Other Name: Upadacitinib

Drug: Placebo for ABT-494
Placebo oral tablet

Drug: Placebo for Adalimumab
Placebo subcutaneous injection

Active Comparator: Adalimumab
It is administered subcutaneously once every two weeks
Drug: Adalimumab
Adalimumab subcutaneous injection

Drug: Placebo for ABT-494
Placebo oral tablet

Experimental: ABT-494 Dose B
It is administered once daily.
Drug: ABT-494
Oral tablet
Other Name: Upadacitinib

Drug: Placebo for Adalimumab
Placebo subcutaneous injection

Placebo Comparator: Placebo followed by ABT-494 Dose A
It is administered once daily.
Drug: ABT-494
Oral tablet
Other Name: Upadacitinib

Drug: Placebo for ABT-494
Placebo oral tablet

Drug: Placebo for Adalimumab
Placebo subcutaneous injection

Experimental: ABT-494 Dose A
It is administered once daily.
Drug: ABT-494
Oral tablet
Other Name: Upadacitinib

Drug: Placebo for Adalimumab
Placebo subcutaneous injection




Primary Outcome Measures :
  1. Proportion of participants achieving American College of Rheumatology (ACR) 20 response [ Time Frame: Week 12 ]
    Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PhGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hsCRP).


Secondary Outcome Measures :
  1. ACR 70 response [ Time Frame: Week 12 ]
    Response defined as at least 70% reduction (improvement) compared with baseline in tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PhGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hsCRP).

  2. Change from baseline in Leeds Dactylitis Index (LDI) [ Time Frame: Week 24 ]
    LDI assesses the presence or absence of dactylitis in all 20 of the subject's digits.

  3. Change from baseline in FACIT-Fatigue Questionnaire [ Time Frame: 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. Participants respond to the questions on a scale from 'not at all' (0) to 'very much' (4). The scale 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.

  4. Change from baseline in Leeds Enthesitis Index (LEI) [ Time Frame: Week 24 ]
    LEI is an enthesitis measure developed specifically for PsA and assesses the presence or absence of tenderness at the following 3 bilateral enthesial sites: medial femoral condyles, lateral epicondyles of the humerus, and Achilles tendon insertions.

  5. ACR 50 response [ Time Frame: Week 12 ]
    Response defined as at least 50% reduction (improvement) compared with baseline in tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PhGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hsCRP).

  6. Proportion of participants achieving a static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline [ Time Frame: Week 16 ]
    The sIGA is a 5 point score ranging from 0 to 4, based on the investigator's assessment of the average elevation, erythema, and scaling of all psoriatic lesions. The assessment is considered "static" which refers to the patients disease state at the time of the assessments, without comparison to any of the patient's previous disease states, whether at Baseline or at a previous visit.

  7. Change from baseline in Patient's Assessment of Pain NRS (superiority of ABT-494 vs. adalimumab) [ Time Frame: Week 12 ]
    Subject will complete the patient's assessment of pain on a numeric rating scale.

  8. Change from baseline in HAQ-DI [ Time Frame: Week 12 ]
    The HAQ DI is a patient-reported questionnaire. It includes the categories of dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. It asks patients about the amount of difficulty they experience in these activities as well as the use of aids and/or devices.

  9. ACR 20 response rate (superiority of ABT-494 vs. adalimumab) [ Time Frame: Week 12 ]
    Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PhGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hsCRP).

  10. ACR 20 response [ Time Frame: Week 2 ]
    Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PhGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hsCRP).

  11. Change from baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Questionnaire [ Time Frame: 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.

  12. Change from baseline in modified PsA Sharp/van der Heijde Score (SHS) [ Time Frame: Week 24 ]
    This will be evaluated through centrally read xray images of bilateral hands and feet.

  13. ACR 20 response rate (non-inferiority of ABT-494 vs adalimumab) [ Time Frame: Week 12 ]
    Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PhGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hsCRP).

  14. Psoriasis Area Severity Index (PASI) 75 response (for participants with >= 3% BSA psoriasis at baseline) [ Time Frame: Week 16 ]
    The percentage of participants with a greater than or equal to 75% reduction (improvement) in Psoriasis Area and Severity Index (PASI) score at Week 12. PASI is a composite measure of the level of erythema (redness of the skin), induration (hardening of the skin), and desquamation (peeling of the skin) on 4 sites (head, upper extremities, trunk, and lower extremities), each of which are rated on a 5-point scale from 0 (no symptoms) to 4 (very marked). The possible range for PASI score is 0 to 72, with the highest score representing complete erythroderma of the severest possible degree; a decrease in score indicates improvement.

  15. Change from baseline in Physical Component Summary (PCS) Score of the Short-Form 36 Health Survey - Version 2 (SF-36v2) [ Time Frame: Week 12 ]
    The SF-36v2 is a general health-related quality of life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument comprises a total of 36 items (questions) targeting a participant's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Domain scores are aggregated into a PCS score (range = 0 to 100; a higher score indicates better mental function and well-being).

  16. Proportion of participants achieving Minimal Disease Activity (MDA) [ Time Frame: Week 24 ]
    The proportion of subjects achieving MDA will be determined based on subjects fulfilling 5 of 7 outcome measures: TJC <= 1; SJC <= 1; PASI <= 1 or BSA-Ps <= 3%; Patient's Assessment of Pain NRS <= 1.5; PtGA-Disease Activity NRS <= 2.0; HAQ-DI score <= 0.5; and tender entheseal points <= 1.

  17. Change from baseline in HAQ-DI (superiority of ABT-494 vs. adalimumab) [ Time Frame: Week 12 ]
    The HAQ DI is a patient-reported questionnaire. It includes the categories of dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. It asks patients about the amount of difficulty they experience in these activities as well as the use of aids and/or devices.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. 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 (MTX, SSZ, LEF, apremilast, bucillamin, cyclosporine 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, 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.

Information from the National Library of Medicine

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): NCT03104400


Contacts
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

  Show 362 Study Locations
Sponsors and Collaborators
AbbVie
Investigators
Study Director: AbbVie Inc. AbbVie

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03104400     History of Changes
Other Study ID Numbers: M15-572
2016-004130-24 ( EudraCT Number )
First Posted: April 7, 2017    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018
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)
Analytic Code
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

Keywords provided by AbbVie:
Arthritis
Psoriasis
Anti-inflammatory
Joint disease
Musculoskeletal disease
Anti-Rheumatic

Additional relevant MeSH terms:
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
Adalimumab
Antirheumatic Agents
Anti-Inflammatory Agents