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Trial record 1 of 1 for:    NCT02706847
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A Study to Compare Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) With an Inadequate Response or Intolerance to Biologic DMARDs (SELECT-BEYOND)

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ClinicalTrials.gov Identifier: NCT02706847
Recruitment Status : Active, not recruiting
First Posted : March 11, 2016
Results First Posted : October 7, 2019
Last Update Posted : March 5, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:

The study objective of Period 1 (Day 1 to Week 24) is to compare the safety and efficacy of 30 mg once daily (QD) and 15 mg QD upadacitinib versus placebo for the treatment of signs and symptoms of participants with moderately to severely active RA who were on a stable dose of csDMARDs and had an inadequate response to or intolerance to at least 1 bDMARD.

The study objective of Period 2 (Week 24 to Week 240) is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 30 mg QD and 15 mg QD in participants with RA who completed Period 1.


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

Detailed Description:

This study includes a 35-day screening period; a 24-week randomized, double-blind, parallel-group, placebo controlled treatment period (Period 1); a 216-week blinded long-term extension period (Period 2); and a 30-day follow-up period (call or visit).

Period 1 consists of a 12-week double-blind, placebo-controlled treatment phase plus a 12-week double-blind phase where all participants were to receive upadacitinib; at Week 12 participants assigned to placebo will be switched to upadacitinib according to their randomization assignment.

Participants who meet eligibility criteria will be randomized in a 2:2:1:1 ratio to one of four treatment groups:

  • Group 1: Upadacitinib 30 mg QD (Day 1 to Week 12) → upadacitinib 30 mg QD (Week 12 and thereafter)
  • Group 2: Upadacitinib 15 mg QD (Day 1 to Week 12) → upadacitinib 15 mg QD (Week 12 and thereafter)
  • Group 3: Placebo (Day 1 to Week 12) → upadacitinib 30 mg QD (Week 12 and thereafter)
  • Group 4: Placebo (Day 1 to Week 12) → upadacitinib 15 mg QD (Week 12 and thereafter) Participants will continue stable dose of csDMARD therapy for the first 24 weeks of the study.

Participants who complete the Week 24 visit (end of Period 1) will enter the blinded long-term extension portion of the study, Period 2 and continue to receive the same dose of upadacitinib per original randomization assignment in a blinded manner. Starting at Week 24, at least 20% improvement in both swollen joint count (SJC) and tender joint count (TJC) compared to Baseline is required to remain on study drug. Starting at Week 24, initiation of or change in corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or adding or increasing doses in up to 2 csDMARDs (concomitant use of up to 2 csDMARDs except the combination of methotrexate and leflunomide) is allowed as per local label.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 499 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 on Stable Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) in Subjects With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response or Intolerance to Biologic DMARDs (bDMARDs)
Actual Study Start Date : March 15, 2016
Actual Primary Completion Date : April 3, 2017
Estimated Study Completion Date : February 2, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Upadacitinib 15 mg

Period 1: Participants receive Upadacitinib 15 mg once daily for 24 weeks.

Period 2: Participants will continue on Upadacitinib 15 mg once daily.

Drug: Upadacitinib
Tablet; Oral
Other Names:
  • ABT-494
  • Rinvoq

Experimental: Upadacitinib 30 mg

Period 1: Participants receive Upadacitinib 30 mg once daily for 24 weeks.

Period 2: Participants will continue on Upadacitinib 30 mg once daily until participants begin to receive Upadacitinib 15 mg once daily.

Drug: Upadacitinib
Tablet; Oral
Other Names:
  • ABT-494
  • Rinvoq

Experimental: Placebo and Upadacitnib 15 mg

Period 1: Participants receive placebo once daily for 12 weeks followed by Upadacitinib 15 mg once daily for 12 weeks.

Period 2: Participants will continue on Upadacitnib 15 mg once daily.

Drug: Upadacitinib
Tablet; Oral
Other Names:
  • ABT-494
  • Rinvoq

Drug: Placebo
Tablet; Oral

Experimental: Placebo and Upadacitnib 30 mg

Period 1: Participants receive placebo once daily for 12 weeks followed by Upadacitinib 30 mg once daily for 12 weeks.

Period 2: Participants will continue on Upadacitinib 30 mg once daily until participants begin to receive Upadacitinib 15 mg once daily.

Drug: Upadacitinib
Tablet; Oral
Other Names:
  • ABT-494
  • Rinvoq

Drug: Placebo
Tablet; Oral




Primary Outcome Measures :
  1. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Baseline and Week 12 ]

    The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:

    1. ≥ 20% improvement in 68-tender joint count;
    2. ≥ 20% improvement in 66-swollen joint count; and
    3. ≥ 20% improvement in at least 3 of the 5 following parameters:

      • Physician global assessment of disease activity
      • Patient global assessment of disease activity
      • Patient assessment of pain
      • Health Assessment Questionnaire - Disability Index (HAQ-DI)
      • High-sensitivity C-reactive protein (hsCRP).

  2. Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 [ Time Frame: Week 12 ]

    The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was low disease activity, based on a Disease Activity Score 28 (DAS28)-CRP score of ≤ 3.2 at Week 12.

    The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.

    A DAS28 score less than or equal to 3.2 indicates low disease activity.



Secondary Outcome Measures :
  1. Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12 [ Time Frame: Baseline and Week 12 ]
    The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline in DAS28 (CRP) indicates improvement in disease activity.

  2. Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 [ Time Frame: Baseline and Week 12 ]

    The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.

    A negative change from Baseline in the overall score indicates improvement.


  3. Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 [ Time Frame: Baseline and Week 12 ]

    The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).

    The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.


  4. Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 [ Time Frame: Baseline and Week 12 ]

    Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria:

    1. ≥ 50% improvement in 68-tender joint count;
    2. ≥ 50% improvement in 66-swollen joint count; and
    3. ≥ 50% improvement in at least 3 of the 5 following parameters:

      • Physician global assessment of disease activity
      • Patient global assessment of disease activity
      • Patient assessment of pain
      • Health Assessment Questionnaire - Disability Index (HAQ-DI)
      • High-sensitivity C-reactive protein (hsCRP).

  5. Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 [ Time Frame: Baseline and Week 12 ]

    Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria:

    1. ≥ 70% improvement in 68-tender joint count;
    2. ≥ 70% improvement in 66-swollen joint count; and
    3. ≥ 70% improvement in at least 3 of the 5 following parameters:

      • Physician global assessment of disease activity
      • Patient global assessment of disease activity
      • Patient assessment of pain
      • Health Assessment Questionnaire - Disability Index (HAQ-DI)
      • High-sensitivity C-reactive protein (hsCRP).

  6. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1 [ Time Frame: Baseline and week 1 ]

    Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:

    1. ≥ 20% improvement in 68-tender joint count;
    2. ≥ 20% improvement in 66-swollen joint count; and
    3. ≥ 20% improvement in at least 3 of the 5 following parameters:

      • Physician global assessment of disease activity
      • Patient global assessment of disease activity
      • Patient assessment of pain
      • Health Assessment Questionnaire - Disability Index (HAQ-DI)
      • High-sensitivity C-reactive protein (hsCRP).



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 to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of rheumatoid arthritis (RA) for≥ 3 months.
  • Treated for ≥ 3 months with ≥ 1 bDMARD therapy, but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration prior to the first dose of study drug.
  • Participant has been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide.
  • Meets both of the following criteria:
  • ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
  • hsCRP ≥ 3mg/L at Screening Visit.

Exclusion Criteria:

  • Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
  • History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms]). Current diagnosis of secondary Sjogren's Syndrome is permitted.

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): NCT02706847


Locations
Show Show 188 study locations
Sponsors and Collaborators
AbbVie
Investigators
Layout table for investigator information
Study Director: AbbVie Inc. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] October 26, 2017
Statistical Analysis Plan  [PDF] June 29, 2017


Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02706847    
Other Study ID Numbers: M13-542
2015-003335-35 ( EudraCT Number )
First Posted: March 11, 2016    Key Record Dates
Results First Posted: October 7, 2019
Last Update Posted: March 5, 2020
Last Verified: February 2020
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.: No
Keywords provided by AbbVie:
Musculoskeletal Disease
Arthritis
Joint Disease
Anti-inflammatory agents
Antirheumatic agents
ABT-494
upadacitinib
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Upadacitinib
Antirheumatic Agents
Janus Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action