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A Study to Evaluate Efficacy and Safety of Upadacitinib in Adults With Axial Spondyloarthritis (SELECT AXIS 2)

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: NCT04169373
Recruitment Status : Active, not recruiting
First Posted : November 19, 2019
Results First Posted : September 21, 2022
Last Update Posted : September 27, 2022
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:

This protocol includes 2 standalone studies with randomization, data collection, analysis and reporting conducted independently.

The main objectives of this protocol are:

  • To evaluate the efficacy of upadacitinib compared with placebo on reduction of signs and symptoms in adults with active axial spondyloarthritis (axSpA) including biologic disease-modifying antirheumatic drug inadequate responders (bDMARD-IR) ankylosing spondylitis (AS) (Study 1) and non-radiographic axial spondyloarthritis (nr-axSpA) (Study 2).
  • To assess the safety and tolerability of upadacitinib in adults with active axSpA including bDMARD-IR AS (Study 1) and nr-axSpA (Study 2).
  • To evaluate the safety and tolerability of upadacitinib in extended treatment in adult participants with active axSpA including bDMARD-IR AS who have completed the Double-Blind Period (Study 1) and nr-axSpA who have completed the Double-Blind Period (Study 2).
  • To evaluate the maintenance of disease control after withdrawal of upadacitinib.

Condition or disease Intervention/treatment Phase
Spondyloarthritis Drug: Upadacitinib Drug: Placebo Phase 3

Detailed Description:

Study 1 (bDMARD-IR AS) is comprised of a 14-week randomized, double-blind, parallel-group, placebo-controlled period (the Double-Blind Period); a 90-week open-label, long-term extension period (the Open-Label Extension Period); and a 30-day Follow-Up Visit (F/U Visit).

Study 2 (nr-axSpA) is comprised of a 52-week randomized, double-blind, parallel-group, placebo-controlled period (the Double-Blind Period); a 52-week open-label, long-term extension period (the Open-Label Extension Period); and a 30-day F/U Visit.

In the Double-Blind Period for both studies, participants are randomized in a 1:1 ratio to receive either upadacitinib or placebo once daily (QD).

Participants in the placebo group switch to upadacitinib 15 mg QD at Week 14 in the Open-Label Extension Period for Study 1 (bDMARD-IR AS) and Week 52 in the Open-Label Extension Period for Study 2 (nr-axSpA).

Participants in remission at Week 104 have the option to enroll in a remission-withdrawal period.

Study M19-944 protocol uses a common screening platform for determining eligibility into Study 1 and Study 2. Each study has its own objectives, hypothesis testing, randomization, data collection, and adequate power for primary and secondary endpoints. Analysis and reporting are conducted separately and independently for each study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 734 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Placebo-Controlled, Double-Blind Program to Evaluate Efficacy and Safety of Upadacitinib in Adult Subjects With Axial Spondyloarthritis Followed by a Remission-Withdrawal Period
Actual Study Start Date : November 26, 2019
Actual Primary Completion Date : September 2, 2021
Estimated Study Completion Date : May 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Study 1: Upadacitinib 15 mg
Participants receive 15 mg upadacitinib orally once a day for 104 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment).
Drug: Upadacitinib
Upadacitinib tablet administered orally
Other Names:
  • ABT-494
  • RINVOQ

Placebo Comparator: Study 1: Placebo
Participants receive matching placebo for 14 weeks and then switch to receive 15 mg upadacitinib orally once a day for 90 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment).
Drug: Upadacitinib
Upadacitinib tablet administered orally
Other Names:
  • ABT-494
  • RINVOQ

Drug: Placebo
Placebo for upadacitinib tablet administered orally

Experimental: Study 2: Upadacitinib 15 mg
Participants receive 15 mg upadacitinib orally once a day for 104 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment).
Drug: Upadacitinib
Upadacitinib tablet administered orally
Other Names:
  • ABT-494
  • RINVOQ

Placebo Comparator: Study 2: Placebo

Participants receive matching placebo for 52 weeks and then switch to receive 15 mg upadacitinib orally once a day for 52 weeks.

Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment).

Drug: Upadacitinib
Upadacitinib tablet administered orally
Other Names:
  • ABT-494
  • RINVOQ

Drug: Placebo
Placebo for upadacitinib tablet administered orally




Primary Outcome Measures :
  1. Study 1: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 14 [ Time Frame: Baseline and Week 14 ]

    ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of > 0 units) in the potential remaining domain:

    • Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);
    • Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
    • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

  2. Study 2: Percentage of Participants Achieving an ASAS40 Response at Week 14 [ Time Frame: Baseline and Week 14 ]

    ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of > 0 units) in the potential remaining domain:

    • Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);
    • Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
    • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).


Secondary Outcome Measures :
  1. Study 1: Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 14 [ Time Frame: Baseline and Week 14 ]

    ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:

    1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 [none] - 10 [very severe])
    2. Patient global assessment of disease activity (NRS score 0 [no activity] - 10 [severe activity])
    3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 [none] - 10 [very severe])
    4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 [0 hours] - 10 [2 or more hours])
    5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.

    The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS include Inactive disease (ASDAS < 1.3) and very high disease (ASDAS > 3.5). A negative change from Baseline score indicates improvement in disease activity.


  2. Study 1: Change From Baseline in Magnetic Resonance Imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) Score for the Spine at Week 14 [ Time Frame: Baseline and Week 14 ]

    In the SPARCC MRI assessment of the spine, the entire spine was evaluated for active inflammation (bone marrow edema). Six discovertebral units (DVU) representing the 6 most abnormal DVUs were selected to calculate the MRI Spine SPARCC score. For each of the 6 DVUs, 3 consecutive sagittal slices were assessed in 4 quadrants to evaluate the extent of inflammation in all three dimensions.

    Each quadrant was scored for the presence (1) or absence (0) of edema. If edema was present in at least one quadrant of a DVU slice, it was also scored for intensity and depth of the edema representing that slice: An additional score of 1 was assigned if an intense signal was seen in any quadrant on a DVU slice. Slices that included a lesion demonstrating continuous increased signal of depth ≥ 1 cm extending from the endplate were scored as an additional 1 per slice.

    The maximum (worst) overall score for all 6 DVUs is 108. A negative change from Baseline indicates improvement.


  3. Study 1: Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Week 14 [ Time Frame: Baseline and Week 14 ]

    The BASDAI assesses disease activity by asking the participant to answer 6 questions (each on an 11 point numeric rating scale [NRS]) pertaining to symptoms experienced for the past week. For Questions 1 to 5 (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10. Lower scores indicate less disease activity.

    A BASDAI 50 response is defined as improvement of 50% or more from Baseline in BASDAI score.


  4. Study 1: Percentage of Participants With an ASAS20 Response at Week 14 [ Time Frame: Baseline and Week 14 ]

    ASAS20 response was defined as an improvement of ≥ 20% and an absolute improvement of ≥ 1 unit (on a scale of 0 to 10) from Baseline in at least 3 of the following 4 domains, with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 units [on a scale of 0 to 10]) in the remaining domain:

    • Patient's global assessment of disease activity, measured on a NRS from 0 (no activity) to 10 (severe activity);
    • Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
    • Function, measured by the BASFI which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related BASDAI NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

  5. Study 1: Percentage of Participants With ASDAS Inactive Disease at Week 14 [ Time Frame: Week 14 ]

    ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:

    1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 [none] - 10 [very severe])
    2. Patient global assessment of disease activity (NRS score 0 [no activity] - 10 [severe activity])
    3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 [none] - 10 [very severe])
    4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 [0 hours] - 10 [2 or more hours])
    5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.

    The overall score ranges from 0 with no defined upper score. ASDAS Inactive Disease is defined as an ASDAS score < 1.3.


  6. Study 1: Change From Baseline in Patient's Assessment of Total Back Pain at Week 14 [ Time Frame: Baseline and Week 14 ]
    Participants assessed their total back pain during the last week on a 0 to 10 numerical rating scale (NRS), where 0 represents no pain and 10 represents most severe pain.

  7. Study 1: Change From Baseline in Patient's Assessment of Nocturnal Back Pain at Week 14 [ Time Frame: Baseline and Week 14 ]
    Participants assessed the amount of back pain at night over the last week on a 0 to 10 NRS, where 0 represents no pain and 10 represents most severe pain.

  8. Study 1: Percentage of Participants With ASDAS Low Disease Activity at Week 14 [ Time Frame: Week 14 ]

    ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:

    1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 [none] - 10 [very severe])
    2. Patient global assessment of disease activity (NRS score 0 [no activity] - 10 [severe activity])
    3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 [none] - 10 [very severe])
    4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 [0 hours] - 10 [2 or more hours])
    5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.

    The overall score ranges from 0 with no defined upper score. ASDAS Low Disease Activity is defined as an ASDAS score < 2.1.


  9. Study 1: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 14 [ Time Frame: Baseline and Week 14 ]
    The Bath Ankylosing Spondylitis Functional Index is a validated index to determine the degree of functional limitation in patients with AS. BASFI consists of 10 questions assessing participants' ability to perform activities such as putting on socks, bending, reaching, getting up from the floor or an armless chair, standing, climbing and other physical activities. Each item is scored on a NRS ranging from 0 (easy to perform an activity) to 10 (impossible to perform an activity). The overall score is the mean of the 10 items and ranges from 0 to 10 with higher scores indicating more functional limitations. A negative change from Baseline in BASFI indicates improvement.

  10. Study 1: Percentage of Participants With ASAS Partial Remission at Week 14 [ Time Frame: Week 14 ]

    ASAS partial remission (PR) is defined as an absolute score of ≤ 2 units on a 0 to 10 scale for each of the four following domains:

    • Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);
    • Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
    • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

  11. Study 1: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score at Week 14 [ Time Frame: Baseline and Week 14 ]

    The ASQoL consists of 18 items related to quality of life, including the impact of pain on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. Each item is answered as yes (scored as 1) or no (scored as 0).

    Scores are summed to obtain the overall score which ranges from 0 to 18, where higher scores indicate a worse quality of life. A negative change from Baseline in ASQoL indicates improvement in quality of life.


  12. Study 1: Change From Baseline in ASAS Health Index at Week 14 [ Time Frame: Baseline and Week 14 ]
    The ASAS health index (HI) measures functioning and health across 17 aspects of health in patients with AS, including pain, emotional functions, sleep, sexual function, mobility, self care, and community life. Each of the 17 questions is answered by the participant as "I agree" (score = 1) or "I disagree" (score = 0). The responses to the 17 dichotomous items are summed up to give a total score ranging from 0 to 17, where a higher score indicates a worse health status. A negative change from Baseline indicates improvement.

  13. Study 1: Change From Baseline in Linear Bath Ankylosing Spondylitis Metrology Index (BASMI[Lin]) at Week 14 [ Time Frame: Baseline and Week 14 ]

    The BASMI is a composite score based on 5 direct measurements of spinal mobility:

    1. cervical rotation (measured in degrees),
    2. tragus to wall distance (in centimeters [cm])
    3. lumbar side flexion (in cm),
    4. lumbar flexion (modified Schober's) (in cm) and
    5. intermalleolar distance (in cm).

    Each measurement is converted to a linear score between 0 and 10. The total BASMI(lin) score is the average of the 5 scores and ranges from 0 to 10; the higher the BASMI(lin) score the more severe the patient's limitation of movement due to their ankylosing spondylitis. A negative change from Baseline indicates improvement.


  14. Study 1: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Week 14 [ Time Frame: Baseline and Week 14 ]
    The MASES evaluation was conducted to assess the presence or absence of enthesitis (inflammation of the entheses, or sites where tendons or ligaments insert into the bone) 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. Each site was scored for presence (1) or absence (0) of enthesitis. The MASES is the sum of the 13 site scores, and ranges from 0 to 13, with higher scores indicating more inflammation of the entheses. A negative change from Baseline indicates improvement.

  15. Study 1: Change From Baseline in MRI SPARCC Score for Sacroiliac Joints at Week 14 [ Time Frame: Baseline and Week 14 ]

    In the SPARCC MRI assessment of the sacroiliac (SI) joints 6 consecutive sacroiliac joint image coronal slices representing the largest proportion of the synovial compartment of the SI joints were assessed for edema, intensity and depth of edema.

    Each SI joint (left and right) was divided into quadrants for a total of 8 SI scoring locations. Each quadrant was scored for the presence (1) or absence (0) of edema, intensity of edema (a score of 1 was assigned for each SI joint (left and right) if an intense signal was seen in any quadrant of that joint for each slice), and a lesion was graded as deep (score of 1) if there was 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 total maximum (worst) score for all SI joints across 6 slices is 72. A negative change from Baseline indicates improvement.


  16. Study 2: Change From Baseline in ASDAS at Week 14 [ Time Frame: Baseline and Week 14 ]

    ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:

    1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 [none] - 10 [very severe])
    2. Patient global assessment of disease activity (NRS score 0 [no activity] - 10 [severe activity])
    3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 [none] - 10 [very severe])
    4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 [0 hours] - 10 [2 or more hours])
    5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.

    The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS include Inactive disease (ASDAS < 1.3) and very high disease (ASDAS > 3.5). A negative change from Baseline score indicates improvement in disease activity.


  17. Study 2: Change From Baseline in MRI SPARCC Score for SI Joints at Week 14 [ Time Frame: Baseline and Week 14 ]

    In the SPARCC MRI assessment of the sacroiliac (SI) joints 6 consecutive sacroiliac joint image coronal slices representing the largest proportion of the synovial compartment of the SI joints were assessed for edema, intensity and depth of edema.

    Each SI joint (left and right) was divided into quadrants for a total of 8 SI scoring locations. Each quadrant was scored for the presence (1) or absence (0) of edema, intensity of edema (a score of 1 was assigned for each SI joint (left and right) if an intense signal was seen in any quadrant of that joint for each slice), and a lesion was graded as deep (score of 1) if there was 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 total maximum (worst) score for all SI joints across 6 slices is 72. A negative change from Baseline indicates improvement.


  18. Study 2: Percentage of Participants With BASDAI 50 Response at Week 14 [ Time Frame: Baseline and Week 14 ]

    The BASDAI assesses disease activity by asking the participant to answer 6 questions (each on an 11 point numeric rating scale [NRS]) pertaining to symptoms experienced for the past week. For Questions 1 to 5 (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10. Lower scores indicate less disease activity.

    A BASDAI 50 response is defined as improvement of 50% or more from Baseline in BASDAI score.


  19. Study 2: Percentage of Participants With ASDAS Inactive Disease at Week 14 [ Time Frame: Week 14 ]

    ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:

    1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 [none] - 10 [very severe])
    2. Patient global assessment of disease activity (NRS score 0 [no activity] - 10 [severe activity])
    3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 [none] - 10 [very severe])
    4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 [0 hours] - 10 [2 or more hours])
    5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.

    The overall score ranges from 0 with no defined upper score. ASDAS Inactive Disease is defined as an ASDAS score < 1.3.


  20. Study 2: Change From Baseline in Patient's Assessment of Total Back Pain at Week 14 [ Time Frame: Baseline and Week 14 ]
    Participants assessed their total back pain during the last week on a 0 to 10 numerical rating scale (NRS), where 0 represents no pain and 10 represents most severe pain.

  21. Study 2: Change From Baseline in Patient's Assessment of Nocturnal Back Pain at Week 14 [ Time Frame: Baseline and Week 14 ]
    Participants assessed the amount of back pain at night over the last week on a 0 to 10 NRS, where 0 represents no pain and 10 represents most severe pain.

  22. Study 2: Percentage of Participants With ASDAS Low Disease Activity at Week 14 [ Time Frame: Week 14 ]

    ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:

    1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 [none] - 10 [very severe])
    2. Patient global assessment of disease activity (NRS score 0 [no activity] - 10 [severe activity])
    3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 [none] - 10 [very severe])
    4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 [0 hours] - 10 [2 or more hours])
    5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.

    The overall score ranges from 0 with no defined upper score. ASDAS Low Disease Activity is defined as an ASDAS score < 2.1.


  23. Study 2: Percentage of Participants With ASAS Partial Remission at Week 14 [ Time Frame: Week 14 ]

    ASAS partial remission (PR) is defined as an absolute score of ≤ 2 units on a 0 to 10 scale for each of the four following domains:

    • Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);
    • Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
    • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

  24. Study 2: Change From Baseline in BASFI at Week 14 [ Time Frame: Baseline and Week 14 ]
    The Bath Ankylosing Spondylitis Functional Index is a validated index to determine the degree of functional limitation in patients with AS. BASFI consists of 10 questions assessing participants' ability to perform activities such as putting on socks, bending, reaching, getting up from the floor or an armless chair, standing, climbing and other physical activities. Each item is scored on a NRS ranging from 0 (easy to perform an activity) to 10 (impossible to perform an activity). The overall score is the mean of the 10 items and ranges from 0 to 10 with higher scores indicating more functional limitations. A negative change from Baseline in BASFI indicates improvement.

  25. Study 2: Change From Baseline in ASQoL at Week 14 [ Time Frame: Baseline and Week 14 ]

    The ASQoL consists of 18 items related to quality of life, including the impact of pain on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. Each item is answered as yes (scored as 1) or no (scored as 0).

    Scores are summed to obtain the overall score which ranges from 0 to 18, where higher scores indicate a worse quality of life. A negative change from Baseline in ASQoL indicates improvement in quality of life.


  26. Study 2: Change From Baseline in ASAS Health Index at Week 14 [ Time Frame: Baseline and Week 14 ]
    The ASAS HI measures functioning and health across 17 aspects of health in patients with AS, including pain, emotional functions, sleep, sexual function, mobility, self care, and community life. Each of the 17 questions is answered by the participant as "I agree" (score = 1) or "I disagree" (score = 0). The responses to the 17 dichotomous items are summed up to give a total score ranging from 0 to 17, where a higher score indicates a worse health status. A negative change from Baseline indicates improvement.

  27. Study 2: Percentage of Participants Achieving an ASAS20 Response at Week 14 [ Time Frame: Baseline and Week 14 ]

    ASAS20 response was defined as an improvement of ≥ 20% and an absolute improvement of ≥ 1 unit (on a scale of 0 to 10) from Baseline in at least 3 of the following 4 domains, with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 units [on a scale of 0 to 10]) in the remaining domain:

    • Patient's global assessment of disease activity, measured on a NRS from 0 (no activity) to 10 (severe activity);
    • Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
    • Function, measured by the BASFI which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related BASDAI NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

  28. Study 2: Change From Baseline in BASMI(Lin) at Week 14 [ Time Frame: Baseline and Week 14 ]

    The BASMI is a composite score based on 5 direct measurements of spinal mobility:

    1. cervical rotation (measured in degrees),
    2. tragus to wall distance (in centimeters [cm])
    3. lumbar side flexion (in cm),
    4. lumbar flexion (modified Schober's) (in cm) and
    5. intermalleolar distance (in cm).

    Each measurement is converted to a linear score between 0 and 10. The total BASMI(lin) score is the average of the 5 scores and ranges from 0 to 10; the higher the BASMI(lin) score the more severe the patient's limitation of movement due to their ankylosing spondylitis. A negative change from Baseline indicates improvement.


  29. Study 2: Change From Baseline in MASES at Week 14 [ Time Frame: Baseline and Week 14 ]
    The MASES evaluation was conducted to assess the presence or absence of enthesitis (inflammation of the entheses, or sites where tendons or ligaments insert into the bone) 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. Each site was scored for presence (1) or absence (0) of enthesitis. The MASES is the sum of the 13 site scores, and ranges from 0 to 13, with higher scores indicating more inflammation of the entheses. A negative change from Baseline indicates improvement.

  30. Study 2: Change From Baseline in MRI SPARCC Score for the Spine at Week 14 [ Time Frame: Baseline and Week 14 ]

    In the SPARCC MRI assessment of the spine, the entire spine is evaluated for active inflammation (bone marrow edema). Six discovertebral units (DVU) representing the 6 most abnormal DVUs were selected to calculate the MRI Spine SPARCC score. For each of the 6 DVUs, 3 consecutive sagittal slices were assessed in 4 quadrants to evaluate the extent of inflammation in all three dimensions.

    Each quadrant was scored for the presence (1) or absence (0) of edema. If edema was present in at least one quadrant of a DVU slice, it was also scored for intensity and depth of the edema representing that slice: An additional score of 1 was assigned if an intense signal was seen in any quadrant on a DVU slice. Slices that included a lesion demonstrating continuous increased signal of depth ≥ 1 cm extending from the endplate were scored as an additional 1 per slice.

    The maximum (worst) overall score for all 6 DVUs is 108. A negative change from Baseline indicates improvement.


  31. Study 2: Percentage of Participants Achieving an ASAS40 Response at Week 52 [ Time Frame: Baseline and Week 52 ]

    ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of > 0 units) in the potential remaining domain:

    • Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity);
    • Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain);
    • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

  32. Study 2: Percentage of Participants Rescued Between Week 24 and Week 52 [ Time Frame: Week 24 through Week 52 ]
    Participants who do not achieve an ASAS20 response at any 2 consecutive scheduled visits will be rescued with standard of care as described in the protocol.

  33. Study 2: Percentage of Participants With ASDAS Major Improvement at Week 52 [ Time Frame: Baseline and Week 52 ]

    ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:

    1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 [none] - 10 [very severe])
    2. Patient global assessment of disease activity (NRS score 0 [no activity] - 10 [severe activity])
    3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 [none] - 10 [very severe])
    4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 [0 hours] - 10 [2 or more hours])
    5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.

    The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS include Inactive disease (ASDAS < 1.3) and very high disease (ASDAS > 3.5). Major Improvement is defined as a change from Baseline of ≤ -2.0.


  34. Study 2: Percentage of Participants With ASDAS Inactive Disease at Week 52 [ Time Frame: Week 52 ]

    ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:

    1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 [none] - 10 [very severe])
    2. Patient global assessment of disease activity (NRS score 0 [no activity] - 10 [severe activity])
    3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 [none] - 10 [very severe])
    4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 [0 hours] - 10 [2 or more hours])
    5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.

    The overall score ranges from 0 with no defined upper score. ASDAS Inactive Disease is defined as an ASDAS score < 1.3.


  35. Study 2: Percentage of Participants With ASDAS Low Disease Activity at Week 52 [ Time Frame: Week 52 ]

    ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula:

    1. Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 [none] - 10 [very severe])
    2. Patient global assessment of disease activity (NRS score 0 [no activity] - 10 [severe activity])
    3. Peripheral pain/swelling (BASDAI Question 3; NRS score 0 [none] - 10 [very severe])
    4. Duration of morning stiffness (BASDAI Question 6; NRS score 0 [0 hours] - 10 [2 or more hours])
    5. High-sensitivity C-reactive protein (hs-CRP) in mg/L.

    The overall score ranges from 0 with no defined upper score. ASDAS Low Disease Activity is defined as an ASDAS score < 2.1.




Information from the National Library of Medicine

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.


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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:

  • Study 1:

    • Must have a clinical diagnosis of ankylosing spondylitis (AS) and meet the modified New York Criteria for AS,
    • Must not have total spinal ankylosis
    • Must have been previously exposed to 1 or 2 bDMARDs (at least 1 tumor necrosis factor [TNF] inhibitor or 1 interleukin [IL]-17 inhibitor [IL-17i]), and must have discontinued the bDMARD therapy due to either lack of efficacy (after at least 12 weeks of treatment with a bDMARD at an adequate dose) or intolerance (irrespective of treatment duration). Prior exposure to two bDMARDs was allowed for no more than 30% of patients; among patients with prior exposure to two bDMARDs, a lack of efficacy to one bDMARD and intolerance to another was permitted, but a patient could not have a lack of efficacy to two bDMARDs
  • Study 2:

    • Must have a clinical diagnosis of nr-axSpA fulfilling the 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA but not meeting the radiologic criterion of the modified New York criteria for AS
    • Must have objective signs of active inflammation consistent with axSpA on magnetic resonance imaging (MRI) of sacroiliac (SI) joints or based on high sensitivity C-reactive protein (hsCRP) > the upper limit of normal (ULN).
    • Prior treatment with at most one bDMARD (either TNF inhibitor or IL-17i) is allowed for at least 20% but no more than 35% of enrolled patients who had to discontinue the prior bDMARD due to either lack of efficacy (after ≥ 12 weeks at an adequate dose) or intolerance (regardless of treatment duration).
  • Must have a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 at the Screening and Baseline Visits.
  • Must have a Total Back Pain score ≥ 4 based on a 0 - 10 numerical rating scale at the Screening and Baseline Visits.
  • Has had an inadequate response to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) over an at least 4-week period in total at maximum recommended or tolerated doses, or has an intolerance to or contraindication for NSAIDs as defined by the Investigator.

Exclusion Criteria:

  • Must not have been exposed to any Janus kinase (JAK) inhibitor (including but not limited to upadacitinib [Rinvoq®], tofacitinib [Xeljanz®], baricitinib [Olumiant®], filgotinib, ruxolitinib [Jakafi®], abrocitinib [PF-04965842], and peficitinib [Smyraf®]).
  • Prior bDMARD therapy must be washed out.
  • Participant must not have a history of an allergic reaction or significant sensitivity to constituents of the study drug.

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): NCT04169373


Locations
Show Show 212 study locations
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: ABBVIE INC. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] July 12, 2021
Statistical Analysis Plan  [PDF] September 15, 2021

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT04169373    
Other Study ID Numbers: M19-944
2019-003229-12 ( EudraCT Number )
First Posted: November 19, 2019    Key Record Dates
Results First Posted: September 21, 2022
Last Update Posted: September 27, 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, analyses plans, 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: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
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 and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
URL: https://vivli.org/ourmember/abbvie/

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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.: Yes
Keywords provided by AbbVie:
Upadacitinib
Axial Spondyloarthritis (axSpA)
Spondyloarthritis
Ankylosing Spondylitis (AS)
Additional relevant MeSH terms:
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Spondylitis
Spondylarthritis
Bone Diseases, Infectious
Infections
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Arthritis
Joint Diseases
Upadacitinib
Janus Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents