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A Study Investigating the Efficacy and Safety of Upadacitinib (ABT-494) Given With Methotrexate (MTX) in Adults With Rheumatoid Arthritis Who Have Had an Inadequate Response to MTX Alone

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: NCT02066389
Recruitment Status : Completed
First Posted : February 19, 2014
Results First Posted : October 4, 2019
Last Update Posted : October 4, 2019
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:
The primary objective of the study was to compare the safety and efficacy of multiple doses of upadacitinib versus placebo in adults with moderately to severely active rheumatoid arthritis (RA) on stable background methotrexate therapy who had not shown an adequate response to methotrexate alone.

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Investigate the Safety and Efficacy of ABT-494 With Background Methotrexate (MTX) in Subjects With Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response to MTX Alone
Actual Study Start Date : March 26, 2014
Actual Primary Completion Date : July 2, 2015
Actual Study Completion Date : July 2, 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Participants received placebo capsules twice daily for 12 weeks.
Drug: Placebo
Tablets for oral administration

Experimental: Upadacitinib 3 mg BID
Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.
Drug: Upadacitinib
Tablets for oral administration
Other Name: ABT-494

Experimental: Upadacitinib 6 mg BID
Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.
Drug: Upadacitinib
Tablets for oral administration
Other Name: ABT-494

Experimental: Upadacitinib 12 mg BID
Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.
Drug: Upadacitinib
Tablets for oral administration
Other Name: ABT-494

Experimental: Upadacitinib 18 mg BID
Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.
Drug: Upadacitinib
Tablets for oral administration
Other Name: ABT-494

Experimental: Upadacitinib 24 mg QD
Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
Drug: Upadacitinib
Tablets for oral administration
Other Name: ABT-494




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

    A participant was a responder if the following 3 criteria for improvement from baseline were met:

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

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

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

    A participant was a responder if the following 3 criteria for improvement from baseline were met:

    • ≥ 70% improvement in tender joint count;
    • ≥ 70% improvement in swollen joint count; and
    • ≥ 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).

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

    The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale (VAS) from 0 to 100 mm). DAS28(CRP) scores range from 0 to approximately 10 where higher scores indicate more disease activity.

    LDA is defined as a DAS28(CRP) score < 3.2.


  4. Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12 [ Time Frame: Week 12 ]

    The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale from 0 to 100 mm). DAS28(CRP) scores range from 0 to 10 where higher scores indicate more disease activity.

    CR is defined as a DAS28(CRP) score < 2.6.


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

    The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.

    LDA is defined as a CDAI score ≤ 10.


  6. Percentage of Participants Achieving Clinical Remission Based on CDAI at Week 12 [ Time Frame: Week 12 ]

    The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.

    CR is defined as a CDAI score ≤ 2.8.




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

Inclusion Criteria:

  1. Diagnosed with RA based on either the 1987-revised American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European League against Rheumatism (EULAR) criteria for ≥ 3 months.
  2. Have active RA as defined by the following minimum disease activity criteria:

    • ≥ 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits.
    • ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
    • high-sensitivity C-reactive protein (hsCRP) > upper limit of normal (ULN) OR positive for both rheumatoid factor and anti-cyclic citrullinated peptide (CCP) at Screening.
  3. Subjects must have been receiving oral or parenteral methotrexate therapy ≥ 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to Baseline Visit. Subjects should also be on a stable dose of folic acid (or equivalent) for at least 4 weeks prior to Baseline Visit. Subjects should continue with their stable doses of methotrexate and folic acid throughout the study.
  4. Except for MTX, subjects must have discontinued all oral disease-modifying anti-rheumatic drugs (DMARDs) prior to Baseline Visit as specified below or for at least five times the mean terminal elimination half-life of a drug, whichever is longer:

    • ≥ 4 weeks prior to Baseline Visit for minocycline, penicillamine, sulfasalazine, hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide
    • ≥ 8 weeks prior to Baseline Visit for leflunomide if no elimination procedure was followed, or adhere to a washout procedure (i.e., 11 days washout with colestyramine, or 30 days washout with activated charcoal)
  5. Subject has a negative tuberculosis (TB) Screening Assessment. If the subject has evidence of a latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis or have documented completion of a full course of TB prophylaxis, prior to Baseline Visit.
  6. Subjects can be taking non-steroidal anti-inflammatory drugs (NSAIDS), acetaminophen, oral corticosteroids (equivalent to prednisone ≤ 10 mg), or inhaled corticosteroids at a stable dose for at least 4 weeks prior to Baseline Visit for stable medical conditions and should be kept at a stable dose throughout the study. NSAIDs, acetaminophen, tramadol, codeine, hydrocodone and propoxyphene taken as needed are allowed but may not be taken 24 hours prior to any study visit. Oral and inhaled corticosteroids taken as needed are allowed but may not be taken 24 hours prior to any study visit.
  7. Subjects must have discontinued high potency opiates including (but not limited to): oxycodone, oxymorphone, fentanyl, levorphanol, buprenorphine, methadone, hydromorphone, and morphine at least 4 weeks prior to Baseline Visit.

Exclusion Criteria:

  1. Female who is pregnant or breastfeeding.
  2. Prior exposure to Janus activated kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib).
  3. Prior exposure to any investigational or approved biologic RA therapy.
  4. Receipt of any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug (whichever is longer) prior to Week 0 Visit.
  5. Current or expected need of other immunosuppressant medications, except methotrexate. Use of oral intake of > 10 mg prednisone/day or equivalent corticosteroid therapy (see inclusion criterion 7).
  6. Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 8 weeks prior to the Week 0 Visit.
  7. Screening laboratory values meeting the following criteria:

    • Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 × ULN
    • Estimated glomerular filtration rate (eGRF) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73 m²
    • Total white blood cell count (WBC) < 3,000/µL
    • Absolute neutrophil count (ANC) < 1,200/µL
    • Platelet count < 100,000/µL
    • Absolute lymphocytes count < 750/ µL
    • Hemoglobin < 9 gm/dL

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): NCT02066389


Locations
Show Show 63 study locations
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02066389    
Other Study ID Numbers: M13-537
2013-003984-72 ( EudraCT Number )
First Posted: February 19, 2014    Key Record Dates
Results First Posted: October 4, 2019
Last Update Posted: October 4, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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 Diseases
anti-inflammatory agents
antirheumatic agents
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
Janus Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents