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A Study Comparing Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have an Inadequate Response to MTX (SELECT-MONOTHERAPY)

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: NCT02706951
Recruitment Status : Active, not recruiting
First Posted : March 11, 2016
Results First Posted : October 7, 2019
Last Update Posted : March 9, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:

The study objective of Period 1 of this study is to compare the safety and efficacy (signs and symptoms) of upadacitinib 30 mg once daily (QD) alone and 15 mg QD alone versus continuing MTX alone adults with moderately to severely active rheumatoid arthritis (RA) with an inadequate response to MTX.

The study objective of Period 2 is to evaluate the long term safety, tolerability, and efficacy of upadacitinib 30 mg QD and 15 mg QD in adults with RA who had completed Period 1.


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

Detailed Description:

The study includes a 35-day screening period; a 14-week randomized, double-blind, parallel-group, controlled treatment period (Period 1); a 226-week blinded extension period (Period 2); and a 30-day follow-up visit.

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

  • Group 1: upadacitinib 30 mg QD (Period 1) → upadacitinib 30 mg QD (Period 2)
  • Group 2: upadacitinib 15 mg QD (Period 1) → upadacitinib 15 mg QD (Period 2)
  • Group 3: MTX (Period 1) → upadacitinib 30 mg QD (Period 2)
  • Group 4: MTX (Period 1) → upadacitinib 15 mg QD (Period 2)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 648 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) Monotherapy to Methotrexate (MTX) in Adults With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response to MTX
Actual Study Start Date : March 23, 2016
Actual Primary Completion Date : October 2, 2017
Estimated Study Completion Date : July 17, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Upadacitinib 30 mg

Period 1: Participants receive Upadacitnib 30 mg once daily and Methotrexate once weekly for 14 weeks.

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

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

Drug: Placebo Methotrexate
Capsule; Oral

Experimental: Upadacitinib 15 mg

Period 1: Participants receive Upadacitnib 15 mg once daily and methotrexate once weekly for 14 weeks.

Period 2: Participants receive Upadacitinib 15 mg once daily.

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

Drug: Placebo Methotrexate
Capsule; Oral

Experimental: Methotrexate followed by Upadacitinib 30 mg

Period 1: Participants receive Methotrexate once weekly and Upadacitinib Placebo once daily for 14 weeks.

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

Drug: Methotrexate
Capsule; Oral

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

Drug: Placebo Upadacitinib
Tablet; Oral

Drug: Placebo Methotrexate
Capsule; Oral

Experimental: Methotrexate followed by Upadacitinib 15 mg

Period 1: Participants receive Methotrexate once weekly and Upadacitinib Placebo for 14 weeks.

Period 2: Participants receive Upadacitinib 15 mg once daily.

Drug: Methotrexate
Capsule; Oral

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

Drug: Placebo Upadacitinib
Tablet; Oral

Drug: Placebo Methotrexate
Capsule; Oral




Primary Outcome Measures :
  1. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 14 [ Time Frame: Baseline and week 14 ]

    The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 14. 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 14 [ Time Frame: Week 14 ]

    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 14.

    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 14 [ Time Frame: Baseline to week 14 ]
    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 Heath Assessment Questionnaire and Disability Index (HAQ-DI) at Week 14 [ Time Frame: Baseline to week 14 ]
    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 14 [ Time Frame: Baseline to week 14 ]

    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 Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 14 [ Time Frame: Week 14 ]

    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 2.6 indicates clinical remission.


  5. Change From Baseline in Duration of Morning Stiffness at Week 14 [ Time Frame: Baseline to week 14 ]
    Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days. A negative change from Baseline indicates improvement.

  6. Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 14 [ Time Frame: Baseline and week 14 ]

    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).

  7. Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 14 [ Time Frame: Baseline and week 14 ]

    Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 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).



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 RA for >= 3 months.
  • Subjects must have been on oral or parenteral MTX therapy >= 3 months and on a stable dose for >= 4 weeks prior to first dose of study drug.
  • Must have discontinued all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) (other than MTX) >= 4 weeks prior to first dose of study drug.
  • Meets the following minimum disease activity criteria: >= 6 swollen joints (based on 66 joint counts) and >= 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.

Exclusion Criteria:

  • Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
  • Prior exposure to any biological disease-modifying anti-rheumatic drugs (bDMARDs).
  • Current diagnosis of inflammatory joint disease other than RA. 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): NCT02706951


Locations
Show Show 153 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 25, 2017
Statistical Analysis Plan  [PDF] November 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: NCT02706951    
Other Study ID Numbers: M15-555
2015-003376-75 ( EudraCT Number )
First Posted: March 11, 2016    Key Record Dates
Results First Posted: October 7, 2019
Last Update Posted: March 9, 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
Upadacitinib
ABT-494
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Upadacitinib
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Janus Kinase Inhibitors
Protein Kinase Inhibitors