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A Study to Compare Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis (RA) Who Are on a Stable Dose of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) and Have an Inadequate Response to csDMARDs (SELECTSUNRISE)

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: NCT02720523
Recruitment Status : Active, not recruiting
First Posted : March 28, 2016
Results First Posted : October 21, 2019
Last Update Posted : July 15, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:

This is a randomized, double-blind study comparing ABT-494 to placebo in Japanese participants with moderately to severely active rheumatoid arthritis who are on a stable dose of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and have an inadequate response.

Following marketing approval of upadacitinib for rheumatoid arthritis in Japan, this study will become a post-marketing clinical study and include a long-term extension period.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Placebo Drug: Upadacitinib Phase 2 Phase 3

Detailed Description:

This study consisted of a 35-day screening period; a 12-week randomized, double-blind, parallel-group, placebo-controlled treatment period (Period 1); a 248-week blinded long-term extension period (Period 2); and a 30-day follow-up period (call or visit).

Participants who met eligibility criteria were randomized in a 3:3:3:1:1:1 ratio to one of six treatment groups:

  • Group 1: Upadacitinib 7.5 mg QD (Period 1) → upadacitinib 7.5 mg QD (Period 2)
  • Group 2: Upadacitinib 15 mg QD (Period 1) → upadacitinib 15 mg QD (Period 2)
  • Group 3: Upadacitinib 30 mg QD (Period 1) → upadacitinib 30 mg QD (Period 2)
  • Group 4: Placebo (Period 1) → upadacitinib 7.5 mg QD (Period 2)
  • Group 5: Placebo (Period 1) → upadacitinib 15 mg QD (Period 2)
  • Group 6: Placebo (Period 1) → upadacitinib 30 mg QD (Period 2)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 197 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2b/3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo in Japanese Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Dose of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) and Have an Inadequate Response to csDMARDs
Actual Study Start Date : March 22, 2016
Actual Primary Completion Date : August 3, 2017
Estimated Study Completion Date : January 14, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Placebo / Upadacitinib 7.5 mg

Period 1: Participants will receive placebo once daily for 12 weeks.

Period 2: Participants will receive Upadacitinib 7.5 mg once daily for 248 weeks.

Drug: Placebo
Tablet; Oral

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

Experimental: Placebo / Upadacitinib 15 mg

Period 1: Participants will receive placebo once daily for 12 weeks.

Period 2: Participants will receive upadacitinib 15 mg once daily for 248 weeks.

Drug: Placebo
Tablet; Oral

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

Experimental: Placebo / Upadacitinib 30 mg

Period 1: Participants will receive placebo once daily for 12 weeks.

Period 2: Participants will receive upadacitinib 30 mg once daily until regulatory approval of RA indication in Japan at which point they will switch to receive upadacitinib 15 mg once daily. Participants will receive upadacitinib for 248 weeks.

Drug: Placebo
Tablet; Oral

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

Experimental: Upadacitinib 7.5 mg / Upadacitinib 7.5 mg

Period 1: Participants will receive upadacitinib 7.5 mg once daily for 12 weeks.

Period 2: Participants will receive upadacitinib 7.5 mg once daily for 248 weeks.

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

Experimental: Upadacitinib 15 mg / Upadacitinib 15 mg

Period 1: Participants will receive upadacitinib 15 mg once daily for 12 weeks.

Period 2: Participants will receive upadacitinib 15 mg once daily for 248 weeks.

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

Experimental: Upadacitinib 30 mg / Upadacitinib 30 mg

Period 1: Participants will receive upadacitinib 30 mg once daily for 12 weeks.

Period 2: Participants will receive upadacitinib 30 mg once daily until regulatory approval of RA indication in Japan at which point they will switch to receive upadacitinib 15 mg once daily. Participants will receive upadacitinib for 248 weeks.

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




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 ]

    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).


Secondary Outcome Measures :
  1. Change From Baseline in Disease Activity Score 28 (DAS28) (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.

  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. 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).

  4. 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).

  5. 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.


  6. Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 [ Time Frame: Week 12 ]
    Low disease activity. was defined as a DAS28 score less than or equal to 3.2. 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.

  7. Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12 [ Time Frame: Week 12 ]
    Clinical remission was defined as a DAS28 (CRP) score less than 2.6. 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.

  8. 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).

  9. Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at Week 12 [ Time Frame: Baseline and Week 12 ]
    The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better quality of life. A positive change from Baseline indicates improvement.

  10. Change From Baseline in Rheumatoid Arthritis Work Instability Scale (RA-WIS) at Week 12 [ Time Frame: Baseline and Week 12 ]

    RA-WIS is a simple validated tool to evaluate work instability (the consequence of a mismatch between an individual's functional ability and their work tasks). RA-WIS consists of 23 questions relating to the participant's functioning in their work environment, each answered as Yes or No. The total score is the number of questions answered Yes, and ranges from 0 to 23.

    A score < 10 means low risk and no action is needed, scores between 10 and 17 indicate medium risk and appropriate advice and information should be given. If the score is > 17, it means high risk and it could warrant referral.

    A negative change from Baseline indicates improvement.


  11. Change From Baseline in the Severity of Morning Stiffness at Week 12 [ Time Frame: Baseline and Week 12 ]
    Morning stiffness severity was determined by the Patient's Assessment of Severity and Duration of Morning Stiffness questionnaire. Participants rated the severity of morning stiffness on awakening over the past 7 days on a scale from 0 (No morning stiffness) to 10 (Worst possible morning stiffness).



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of rheumatoid arthritis (RA) for >= 3 months who also fulfill the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA.
  • Subjects have been receiving conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy >= 3 months and on a stable dose for >= 4 weeks prior to the first dose of study drug.
  • Subject has >= 6 swollen joints (based on 66 joint counts) and >= 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
  • Subjects with prior exposure to at most one biological disease-modifying anti-rheumatic drug (bDMARD) may be enrolled (up to 20% of total number of subjects) after the required washout period. Specifically, prior to enrollment:

    1. Subjects with limited exposure to bDMARD (< 3 months) OR
    2. Subjects who are responding to bDMARD therapy but had to discontinue due to intolerability (regardless of treatment duration).

Exclusion Criteria:

  • Prior exposure to any Janus kinase (JAK) inhibitor
  • Subjects who are considered inadequate responders (lack of efficacy) to bDMARD therapy, after minimum 3 months treatment, as determined by the Investigator.
  • 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 [SpA] including ankylosing spondylitis and non-radiographic axial SpA, 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): NCT02720523


Locations
Show Show 50 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] February 23, 2018
Statistical Analysis Plan  [PDF] August 31, 2017

Additional Information:
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02720523    
Other Study ID Numbers: M14-663
First Posted: March 28, 2016    Key Record Dates
Results First Posted: October 21, 2019
Last Update Posted: July 15, 2020
Last Verified: June 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: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AbbVie:
rheumatoid arthritis
ABT-494
Japanese
Antirheumatic agents
Additional relevant MeSH terms:
Layout table for MeSH terms
Upadacitinib
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Janus Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents