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A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04169373
Recruitment Status : Recruiting
First Posted : November 19, 2019
Last Update Posted : November 27, 2019
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 adult participants 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 adult participants with active axSpA including bDMARD-IR AS (Study 1) and with nr-axSpA (Study 2).

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 690 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
Actual Study Start Date : November 15, 2019
Estimated Primary Completion Date : June 6, 2022
Estimated Study Completion Date : March 26, 2024

Arm Intervention/treatment
Experimental: Study 1: Upadacitinib
Participants will be administered upadacitinib for 104 weeks
Drug: Upadacitinib
Upadacitinib is administered as oral tablet
Other Names:
  • ABT-494
  • RINVOQ

Experimental: Study 1: Placebo
Participants will be administered placebo for 14 weeks followed by upadacitinib for 90 weeks
Drug: Upadacitinib
Upadacitinib is administered as oral tablet
Other Names:
  • ABT-494
  • RINVOQ

Drug: Placebo
Placebo for upadacitinib is administered as oral tablet

Experimental: Study 2: Upadacitinib
Participants will be administered upadacitinib for 104 weeks
Drug: Upadacitinib
Upadacitinib is administered as oral tablet
Other Names:
  • ABT-494
  • RINVOQ

Experimental: Study 2: Placebo
Participants will be administered placebo for 52 weeks followed by upadacitinib for 52 weeks
Drug: Upadacitinib
Upadacitinib is administered as oral tablet
Other Names:
  • ABT-494
  • RINVOQ

Drug: Placebo
Placebo for upadacitinib is administered as oral tablet




Primary Outcome Measures :
  1. Study 1: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) 40 Response [ Time Frame: Baseline (Week 0) through Week 14 ]
    ASAS40 is defined as a >= 40% improvement and an absolute improvement of ≥ 2 units (on a scale of 0 to 10; 0 = no pain and 10 = worst possible pain) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no worsening at all in the remaining domain.

  2. Study 2: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) 40 Response [ Time Frame: Baseline (Week 0) through Week 14/Week 52 ]
    ASAS40 is defined as a >= 40% improvement and an absolute improvement of ≥ 2 units (on a scale of 0 to 10; 0 = no pain and 10 = worst possible pain) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no worsening at all in the remaining domain.


Secondary Outcome Measures :
  1. Study 1: Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) [ Time Frame: Baseline (Week 0) through Week 14 ]
    The ASDAS is a composite index with proven validity and reliability to assess disease activity in AS patients. It combines the following 5 disease activity variables: back pain, duration of morning stiffness, patient's global assessment (PtGA), peripheral pain/swelling, and high-sensitivity C-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).

  2. Study 1: Change From Baseline in Magnetic Resonance Imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) Score (Spine) [ Time Frame: Baseline (Week 0) through Week 14 ]
    SPARCC scores for spine are calculated by adding up the dichotomous outcomes from evaluations of the presence, depth, and intensity of bone marrow edema lesions of the spine.

  3. Study 1: Percentage of Participants With ASAS Partial Remission (PR) [ Time Frame: Baseline (Week 0) through Week 14 ]
    ASAS PR is defined as an absolute score of <= 2 units (on a scale of 0 to 10; 0 = no pain and 10 = worst possible pain) from Baseline for each of 4 domains (patient's global assessment, back pain, function and inflammation).

  4. Study 1: Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response [ Time Frame: Baseline (Week 0) through Week 14 ]
    BASDAI 50 response is defined as at least 50% improvement from Baseline in the BASDAI. The BASDAI is a commonly used measure to define disease activity levels in axSpA patients. It consists of a 1 through 10 scale (1 being no problem and 10 being the worst problem) and is used to answer 6 questions pertaining to the 5 major symptoms of AS: Fatigue, Spinal pain, Joint pain/swelling, Areas of localized tenderness, Morning stiffness duration, and Morning stiffness severity.

  5. Study 1: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) [ Time Frame: Baseline (Week 0) through Week 14 ]
    The BASFI is a validated patient reported outcome (PRO) instrument for use in the AS patient population. It consists of 10 items assessing ability to perform activities known to be problematic to AS patients such as dressing, bending, reaching, turning, and climbing steps. The total scores range from 0 to 10.

  6. Study 1: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) [ Time Frame: Baseline (Week 0) through Week 14 ]
    The ASQoL is an 18-item axSpA-specific Quality of Life (QoL) PRO measure validated in the AS patient population. Concepts measured include activities of daily life, emotional functioning, pain, fatigue, and sleep problems. Each item on ASQoL is given a score of "1" or "0," where a score of "1" is given when an item is affirmed indicating adverse QoL. Total scores can range from 0 (good QoL) to 18 (poor QoL).

  7. Study 1: Change From Baseline in ASAS Health Index (HI) [ Time Frame: Baseline (Week 0) through Week 14 ]
    The ASAS HI is validated for patients with all forms of axSpA. It consists of 17 items measuring aspects of functioning, health, and 9 environmental factors that are typical and relevant for these patients. Items are scored dichotomously and assess pain, emotional function, sleep, sexual function, mobility, self-care, and community life. Total scores range from 0 (good health) to 17 (poor health), with lower scores indicating better health.

  8. Study 1: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) [ Time Frame: Baseline (Week 0) through Week 14 ]
    The MASES evaluation will be conducted by a qualified assessor at the visits specified to assess the presence or absence of enthesitis at 13 different sites noting the participant's responses.

  9. Study 1: Change From Baseline in Linear Bath Ankylosing Spondylitis Metrology Index (BASMIlin) [ Time Frame: Baseline (Week 0) through Week 14 ]
    The BASMIlin will be conducted at the visits specified to evaluate spinal mobility in a participant. The site should make every attempt to have the same qualified Investigator or designee conduct these assessments throughout a study for any given participant.

  10. Study 1: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) 20 Response [ Time Frame: Baseline (Week 0) through Week 14 ]
    ASAS20 is defined as a >= 20% improvement and an absolute improvement of >= 1 units (on a scale of 0 to 10; 0 = no pain and 10 = worst possible pain) from Baseline in at least 3 of the 4 domains (patient's global assessment, pain, function and inflammation) with no deterioration in the remaining domain (where deterioration is defined as a worsening of >= 20% and a net worsening of >= 1 unit [on a scale of 0 to 10]).

  11. Study 1: Change From Baseline in MRI SPARCC Score (SI Joints) [ Time Frame: Baseline (Week 0) through Week 14 ]
    SPARCC scores for sacroiliac (SI) joints are calculated by adding up the dichotomous outcomes from evaluations of the presence, depth, and intensity of bone marrow edema lesions of the SI joints.

  12. Study 2: Change From Baseline in ASDAS [ Time Frame: Baseline (Week 0) through Week 14 ]
    The ASDAS is a composite index with proven validity and reliability to assess disease activity in AS patients. It combines the following 5 disease activity variables: back pain, duration of morning stiffness, patient's global assessment (PtGA), peripheral pain/swelling, and high-sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).

  13. Study 2: Change From Baseline in MRI SPARCC Score (SI Joints) [ Time Frame: Baseline (Week 0) through Week 14 ]
    SPARCC scores for sacroiliac (SI) joints are calculated by adding up the dichotomous outcomes from evaluations of the presence, depth, and intensity of bone marrow edema lesions of the SI joints.

  14. Study 2: Percentage of Participants With BASDAI 50 Response [ Time Frame: Baseline (Week 0) through Week 14 ]
    BASDAI 50 response is defined as at least 50% improvement from Baseline in the BASDAI. The BASDAI is a commonly used measure to define disease activity levels in axSpA patients. It consists of a 1 through 10 scale (1 being no problem and 10 being the worst problem) and is used to answer 6 questions pertaining to the 5 major symptoms of AS: Fatigue, Spinal pain, Joint pain/swelling, Areas of localized tenderness, Morning stiffness duration, and Morning stiffness severity.

  15. Study 2: Percentage of Participants With ASAS PR [ Time Frame: Baseline (Week 0) through Week 14 ]
    ASAS PR is defined as an absolute score of <= 2 units (on a scale of 0 to 10; 0 = no pain and 10 = worst possible pain) from Baseline for each of 4 domains (patient's global assessment, pain, function and inflammation).

  16. Study 2: Change From Baseline in BASFI [ Time Frame: Baseline (Week 0) through Week 14 ]
    The BASFI is a validated patient reported outcome (PRO) instrument for use in the AS patient population. It consists of 10 items assessing ability to perform activities known to be problematic to AS patients such as dressing, bending, reaching, turning, and climbing steps. The total scores range from 0 to 10.

  17. Study 2: Change From Baseline in ASQoL [ Time Frame: Baseline (Week 0) through Week 14 ]
    The ASQoL is an 18-item axSpA-specific Quality of Life (QoL) PRO measure validated in the AS patient population. Concepts measured include activities of daily life, emotional functioning, pain, fatigue, and sleep problems. Each item on ASQoL is given a score of "1" or "0," where a score of "1" is given when an item is affirmed indicating adverse QoL. Total scores can range from 0 (good QoL) to 18 (poor QoL).

  18. Study 2: Change From Baseline in ASAS HI [ Time Frame: Baseline (Week 0) through Week 14 ]
    The ASAS HI is validated for patients with all forms of axSpA. It consists of 17 items measuring aspects of functioning, health, and 9 environmental factors that are typical and relevant for these patients. Items are scored dichotomously and assess pain, emotional function, sleep, sexual function, mobility, self-care, and community life. Total scores range from 0 (good health) to 17 (poor health), with lower scores indicating better health.

  19. Study 2: Change From Baseline in MASES [ Time Frame: Baseline (Week 0) through Week 14 ]
    The MASES evaluation will be conducted by a qualified assessor at the visits specified to assess the presence or absence of enthesitis at 13 different sites noting the participant's responses.

  20. Study 2: Change From Baseline in BASMIlin [ Time Frame: Baseline (Week 0) through Week 14 ]
    The BASMIlin will be conducted at the visits specified to evaluate spinal mobility in a participant. The site should make every attempt to have the same qualified Investigator or designee conduct these assessments throughout a study for any given participant.

  21. Study 2: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) 20 Response [ Time Frame: Baseline (Week 0) through Week 14 ]
    ASAS20 is defined as a >= 20% improvement and an absolute improvement of >= 1 units (on a scale of 0 to 10; 0 = no pain and 10 = worst possible pain) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no deterioration in the remaining domain (where deterioration is defined as a worsening of >= 20% and a net worsening of >= 1 unit [on a scale of 0 to 10]).

  22. Study 2: Percentage of Participants Rescued Between Week 24 and Week 52 [ Time Frame: Up to 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.

  23. Study 2: Change From Baseline in Magnetic Resonance Imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) Score (Spine) [ Time Frame: Baseline (Week 0) through Week 14 ]
    SPARCC scores for spine are calculated by adding up the dichotomous outcomes from evaluations of the presence, depth, and intensity of bone marrow edema lesions of the spine.



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: Participant has the clinical diagnosis of ankylosing spondylitis (AS) who meet the modified New York Criteria for AS (Study 1); OR
  • Study 2: Participant has the clinical diagnosis of nr-axSpA fulfilling the 2009 ASAS classification criteria for axSpA but not meeting the radiologic criterion of the modified New York criteria for AS and have objective signs of active inflammation on magnetic resonance imaging (MRI) or based on high sensitivity C-reactive protein (CRP).
  • Study 1 and Study 2: Participant must have 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 numerical rating scale at the Screening and Baseline Visits.
  • Study 1: Participants must have discontinued 1 biologic disease-modifying antirheumatic drug (bDMARD).
  • Study 2: Participant with prior treatment with bDMARD-therapy is allowed.

Exclusion Criteria:

  • Participant must not have been exposed to Janus Kinase (JAK) inhibitor.
  • Prior bDMARD therapy has to 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


Contacts
Layout table for location contacts
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

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Sponsors and Collaborators
AbbVie
Investigators
Layout table for investigator information
Study Director: AbbVie Inc. AbbVie

Additional Information:
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT04169373     History of Changes
Other Study ID Numbers: M19-944
2019-003229-12 ( EudraCT Number )
First Posted: November 19, 2019    Key Record Dates
Last Update Posted: November 27, 2019
Last Verified: November 2019
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

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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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Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Arthritis
Joint Diseases