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A Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis ( SELECT Axis 1 ) (SELECT Axis 1)

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ClinicalTrials.gov Identifier: NCT03178487
Recruitment Status : Recruiting
First Posted : June 7, 2017
Last Update Posted : August 1, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:
This is a Phase 2/3 multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of upadacitinib in participants with active ankylosing spondylitis (AS).

Condition or disease Intervention/treatment Phase
Ankylosing Spondylitis (AS) Drug: Upadacitinib Drug: Upadacitinib Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis
Actual Study Start Date : October 24, 2017
Estimated Primary Completion Date : December 14, 2018
Estimated Study Completion Date : October 22, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Participants receiving Upadacitinib dose A
Participants receiving Upadacitinib dose A once daily.
Drug: Upadacitinib
Tablet
Other Name: ABT-494

Placebo Comparator: Participants receiving placebo
Participants receiving placebo
Drug: Upadacitinib Placebo
Tablet




Primary Outcome Measures :
  1. Proportion of participants with Assessment of SpondyloArthritis international Society (ASAS) 40 response [ Time Frame: At Week 14 ]

    It is defined as a >= 40% improvement and an absolute improvement of >= 2 units (on a scale of 0 to 10) from Baseline in at least three of the following four domains, with no worsening at all in the remaining domain:

    1. Patient's Global Assessment
    2. Pain
    3. Function
    4. Inflammation


Secondary Outcome Measures :
  1. Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) [ Time Frame: Week 0 (baseline) and Week 14 ]
    The BASFI is a participant-reported measure that evaluates physical function.

  2. Proportion of participants with ASAS partial remission (PR) [ Time Frame: Week 14 ]
    ASAS PR is defined as an absolute score of <= 2 units for each of the four domains (patient's global assessment, pain, function and inflammation) identified in ASAS 40.

  3. Change from Baseline in Work Productivity and Activity Impairment (WPAI) [ Time Frame: Week 0 (baseline) and Week 14 ]
    The WPAI is a questionnaire used to evaluate lost productivity.

  4. Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) [ Time Frame: Week 0 (baseline) and Week 14 ]
    The MASES evaluation will be conducted to assess the presence or absence of enthesitis at 13 different sites (first costochondral joint left/right, seventh costochondral joint left/right, posterior superior iliac spine left/right, anterior superior iliac spine left/right, iliac crest left/right, fifth lumbar spinous process, and proximal insertion of Achilles tendon left/right), noting the participants' responses.

  5. Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) [ Time Frame: Week 0 (baseline) and Week 14 ]
    The ASDAS tool is a self-administered questionnaire plus an objective laboratory evaluation.

  6. Change from Baseline in Linear Bath Ankylosing Spondylitis Metrology Index (BASMIlin) [ Time Frame: Week 0 (baseline) and Week 14 ]
    The BASMIlin will be conducted to evaluate spinal mobility in a participant

  7. ASAS 20 response [ Time Frame: At Week 14 ]

    ASAS 20 response is defined as an improvement of >= 20% and absolute improvement of >= 1 unit (on a scale of 0 to 10) from Baseline in at least three of the following four domains, with no deterioration (where deterioration is defined as a worsening of >= 20% and a net worsening of >= 1 units [on a scale of 0 to 10]) in the remaining domain:

    1. Patient's Global Assessment
    2. Pain
    3. Function
    4. Inflammation

  8. Change from Baseline in magnetic resonance imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) score (Spine) [ Time Frame: Week 0 (baseline) and Week 14 ]
    Six discovertebral units (DVU) representing the 6 most abnormal DVUs, and 3 consecutive sagittal slices at each DVU representing the most abnormal slices for that DVU are selected for scoring. Each DVU is divided into 4 quadrants and scored for the presence (1) or absence (0) of edema. The maximum score is 12 per DVU. The maximum score is 72 for 6 DVUs. If edema is present in at least 1 quadrant of a DVU slice, it is scored for intensity and depth of the edema representing that slice: A score of 1 is assigned if an intense signal were to be seen in any quadrant on a DVU slice. The maximum score for intensity per slice is 1, per DVU is 3 and for 6 DVUs is 18. A lesion is graded as deep (1) if there is a homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the surface of the endplate in any quadrant. The maximum score per slice is 1, for a DVU is 3 and for 6 DVUs is 18. The total maximum SPARCC score for all 6 DVUs is 108.

  9. Change from Baseline in Ankylosing Spondylitis (AS) Quality of Life (QoL) [ Time Frame: Week 0 (baseline) and Week 14 ]
    This assess QOL in participants with AS.

  10. Proportion of participants with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response [ Time Frame: At Week 14 ]
    BASDAI 50 response is defined as 50% improvement in the Bath AS Disease Activity Index.

  11. Change from Baseline in ASAS Health Index (HI) [ Time Frame: Week 0 (baseline) and Week 14 ]
    This is used to asses overall functioning.

  12. Change from Baseline in MRI Spondyloarthritis Research Consortium of Canada (SPARCC) score Sacroiliac (SI) joints [ Time Frame: At Week 14 ]
    Six consecutive sacroiliac (SI) joint image coronal slices representing the largest proportion of the synovial compartment of the SI joints are assessed for edema, intensity and depth of edema using SPARCC scoring. Each SI joint (left and right) is divided into quadrants for a total of 8 SI scoring locations. Each quadrant is scored for the presence (1) or absence (0) of edema; the maximum score is 8 per slice and maximum score for 6 SI joint slices is 48. Intensity of edema: A score of 1 is assigned for each SI joint (left and right) if an intense signal is seen in any quadrant of that joint for each slice. The maximum score is 2 per slice and 12 for 6 slices. A lesion is graded as deep (score of 1) if there is a homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the articular surface of the SI joint in any quadrant. The maximum score per slice is 2 and for 6 slices 12. The total maximum score for all SI joints across 6 slices is 72.



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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:

  • Participant with a clinical diagnosis of Ankylosing Spondylitis (AS) and meeting the modified New York Criteria for AS.
  • Participant must have baseline disease activity as defined by having a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >= 4 and a Patient's Assessment of Total Back Pain score >= 4 based on a 0 - 10 Numeric Rating Scale (NRS) at the Screening and Baseline Visits.
  • Participant has had an inadequate response to at least two Nonsteroidal Anti-inflammatory Drugs (NSAIDs) over an at least 4-week period in total at maximum recommended or tolerated doses, or participant has an intolerance to or contraindication for NSAIDs as defined by the Investigator.
  • If entering the study on concomitant Methotrexate (MTX), leflunomide, Sulfasalazine (SSZ), and/or hydroxychloroquine, participant must be on a stable dose of MTX (<= 25 mg/week) and/or SSZ (<= 3 g/day) and/or hydroxychloroquine (<= 400 mg/day) or leflunomide (<= 20 mg/day) for at least 28 days prior to the Baseline Visit. A combination of up to two background conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is allowed except the combination of MTX and leflunomide.
  • If entering the study on concomitant oral corticosteroids, participant must be on a stable dose of prednisone (<= 10 mg/day), or oral corticosteroid equivalents, for at least 14 days prior to the Baseline Visit.
  • If entering the study on concomitant NSAIDs, tramadol, combination of acetaminophen and codeine or hydrocodone, and/or non-opioid analgesics, participant must be on stable dose(s) for at least 14 days prior to the Baseline Visit.

Exclusion Criteria:

  • Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
  • Prior exposure to any biologic therapy with a potential therapeutic impact on spondyloarthritis (SpA).
  • Intra-articular joint injections, spinal/paraspinal injection(s), or parenteral administration of corticosteroids within 28 days prior to the Baseline Visit. Inhaled or topical corticosteroids are allowed.
  • Participant on any other DMARDs (other than those allowed), thalidomide or apremilast within 28 days or five half-lives (whichever is longer) of the drug prior to the Baseline Visit.
  • Participant on opioid analgesics (except for combination acetaminophen/codeine or acetaminophen/hydrocodone which are allowed) or use of inhaled marijuana within 14 days prior to the Baseline Visit.
  • Participant has a history of inflammatory arthritis of different etiology other than axial SpA (including but not limited to rheumatoid arthritis, psoriatic arthritis, mixed connective tissue disease, systemic lupus erythematosus, reactive arthritis, scleroderma, polymyositis, dermatomyositis, fibromyalgia, or any arthritis with onset prior to 17 years of age.
  • Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug: serum aspartate transaminase > 2 × Upper Limit of Normal (ULN); serum alanine transaminase > 2 × ULN; estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease formula < 40 milliliter (mL)/minute/1.73m^2; hemoglobin < 10 gram/deciliter, total white blood cell count < 2,500/microliter (μL); absolute neutrophil count < 1,500/μL; absolute lymphocyte count < 800/μL; and platelet count < 100,000/μL.

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): NCT03178487


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

  Show 105 Study Locations
Sponsors and Collaborators
AbbVie
Investigators
Study Director: AbbVie Inc. AbbVie

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03178487     History of Changes
Other Study ID Numbers: M16-098
2017-000431-14 ( EudraCT Number )
First Posted: June 7, 2017    Key Record Dates
Last Update Posted: August 1, 2018
Last Verified: July 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:
Upadacitinib
ABT-494
Ankylosing Spondylitis (AS)
Safety
Efficacy

Additional relevant MeSH terms:
Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis