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

July 28, 2021 updated by: AbbVie

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

300

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Plovdiv, Bulgaria, 4000
        • MHAT Trimontsium /ID# 127311
      • Plovdiv, Bulgaria, 4000
        • UMHAT Pulmed OOD /ID# 127307
      • Plovdiv, Bulgaria, 4001
        • MHAT Kaspela /ID# 127315
      • Sofia, Bulgaria, 1612
        • Diagnostic Consultative Center /ID# 127313
      • Sofia, Bulgaria, 1612
        • UMHAT Sv. Ivan Rilski /ID# 127314
      • Sofia, Bulgaria, 1612
        • UMHAT Sv. Ivan Rilski /ID# 131608
      • Varna, Bulgaria, 9000
        • Diagnostic Consultative Center /ID# 127312
  • Chile
      • Osorno, Chile, 1710216
        • Corp de Beneficencia Osorno /ID# 127337
      • Puerto Varas, Chile, 5550170
        • Quantum Research LTDA. /ID# 127338
  • Czechia
      • Bruntál, Czechia, 79201
        • Revmatologie Bruntal, s.r.o /ID# 126881
      • Ostrava, Czechia, 722 00
        • Artroscan s.r.o. /ID# 126845
    • Praha 2
      • Prague 2, Praha 2, Czechia, 128 00
        • Revmatologicky ustav Praha /ID# 127317
    • Praha 4
      • Prague 4, Praha 4, Czechia, 140 00
        • Nuselská poliklinika, Revmatologie /ID# 127318
  • Hungary
      • Veszprém, Hungary, 8200
        • Veszprem Megyei Csolnoky Feren /ID# 126876
    • Pest
      • Budapest III, Pest, Hungary, 1036
        • Qualiclinic Kft. /ID# 127340
  • Israel
      • Ashkelon, Israel, 78278
        • Barzilai Medical Center /ID# 126875
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus /ID# 127341
      • Ramat Gan, Israel, 5262100
        • Sheba Medical Center /ID# 126878
  • Latvia
      • Adazi, Latvia, 2164
        • LTD M&M Centers /ID# 127346
      • Baldone, Latvia, 2125
        • Arija's Ancane's Family Doctor /ID# 127342
      • Riga, Latvia, 1005
        • Clinic ORTO /ID# 127345
  • Mexico
      • Mexico City, Mexico, 06090
        • Hospital de Jesús Nazareno /ID# 127352
      • Mexico City, Mexico, 06700
        • Cliditer SA de CV /ID# 127347
      • Mexico City, Mexico, 06700
        • Clinstile, S.A. de C.V. /ID# 127350
  • Poland
    • Lubelskie
      • Lublin, Lubelskie, Poland, 20-607
        • REUMED Sp.z o.o. Filia nr 1 /ID# 127353
    • Malopolskie
      • Krakow, Malopolskie, Poland, 30-002
        • Centrum Medyczne Pratia Krakow /ID# 127358
    • Mazowieckie
      • Warsaw, Mazowieckie, Poland, 00-465
        • NBR Polska /ID# 127359
      • Warsaw, Mazowieckie, Poland, 01-869
        • Medica Pro Familia S.A Warszawa /ID# 127361
    • Podlaskie
      • Białystok, Podlaskie, Poland, 15-099
        • Gabinet Internistyczno Reum. /ID# 127357
    • Pomorskie
      • Gdynia, Pomorskie, Poland, 81-338
        • Centrum Medyczne Pratia Gdynia /ID# 127360
    • Warminsko-mazurskie
      • Elbląg, Warminsko-mazurskie, Poland, 82-300
        • Michal Bazela Higher-Med /ID# 127355
  • Puerto Rico
      • San Juan, Puerto Rico, 00909
        • GCM Medical Group /ID# 127363
  • Russian Federation
      • St. Petersburg, Russian Federation, 192242
        • II Dzhan Research Center /ID# 127376
    • Tatarstan, Respublika
      • Kazan, Tatarstan, Respublika, Russian Federation, 420103
        • City Clinical Hospital #7 /ID# 127372
    • Tverskaya Oblast
      • Tver, Tverskaya Oblast, Russian Federation, 170036
        • Tver Regional Clinical Hosp. /ID# 127375
  • Slovakia
      • Martin, Slovakia, 036 01
        • MEDMAN s.r.o. /ID# 127381
      • Senica, Slovakia, 905 01
        • Poliklinika Senica /ID# 127396
  • South Africa
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7500
        • Panorama Medical Centre /ID# 126846
      • Stellenbosch, Western Cape, South Africa, 7600
        • Winelands Medical Research Ctr /ID# 126844
  • Spain
      • Barcelona, Spain, 08006
        • Hospital Plató /ID# 127384
      • Barcelona, Spain, 08034
        • Hospital CIMA Sanitas /ID# 127383
      • Bilbao, Spain, 48013
        • Hospital Universitario Basurto /ID# 127391
      • Madrid, Spain, 28040
        • Hospital Clin Univ San Carlos /ID# 127382
      • Santiago de Compostela, Spain, 15702
        • Clinica Gaias /ID# 127386
      • Sevilla, Spain, 41010
        • Hospital Infanta Luisa /ID# 127389
      • Sevilla, Spain, 41014
        • Hospital Universitario de Valm /ID# 127387
    • Malaga
      • Málaga, Malaga, Spain, 29009
        • Hospital Regional de Malaga /ID# 127385
  • Turkey
      • Istanbul, Turkey, 34000
        • Medeniyet Univ. Goztepe Traini /ID# 132396
  • Ukraine
      • Kiev, Ukraine, 02125
        • Kiev Municipal Clin Hosp 3 /ID# 127419
      • Kiev, Ukraine, 03680
        • NSC-Strazhesko Ist Cardiology /ID# 127416
      • Sumy, Ukraine, 40000
        • Sumy State University /ID# 127418
  • United States
    • California
      • Hemet, California, United States, 92543
        • C.V. Mehta MD, Med Corporation /ID# 126380
    • Florida
      • DeBary, Florida, United States, 32713-2260
        • Omega Research Consultants, LLC /ID# 125780
      • Venice, Florida, United States, 34292
        • Lovelace Scientific Resources /ID# 127324
    • Georgia
      • Lawrenceville, Georgia, United States, 30045
        • North Georgia Rheumatology Grp /ID# 125779
    • Kansas
      • Wichita, Kansas, United States, 67205
        • PRN Professional Research Network of Kansas, LLC /ID# 126148
    • Maryland
      • Wheaton, Maryland, United States, 20902
        • The Center for Rheumatology & /ID# 127323
    • New Jersey
      • Clifton, New Jersey, United States, 07012
        • Summit Medical Group /ID# 125776
    • New Mexico
      • Las Cruces, New Mexico, United States, 88011
        • Arthritis and Osteo Assoc /ID# 134994
    • Pennsylvania
      • Duncansville, Pennsylvania, United States, 16635
        • Altoona Ctr Clinical Res /ID# 125777
      • Wyomissing, Pennsylvania, United States, 19610
        • Emkey Arthritis and Osteo Clin /ID# 134716
    • Texas
      • Houston, Texas, United States, 77034
        • Accurate Clinical Research /ID# 126535
    • West Virginia
      • Clarksburg, West Virginia, United States, 26301
        • Mountain State Clinical Resear /ID# 127089

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 96 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • ABT-494

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Baseline and Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Baseline and Week 12
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).
Baseline and Week 12
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.
Week 12
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.
Week 12
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.
Week 12
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.
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 26, 2014

Primary Completion (Actual)

July 2, 2015

Study Completion (Actual)

July 2, 2015

Study Registration Dates

First Submitted

February 17, 2014

First Submitted That Met QC Criteria

February 17, 2014

First Posted (Estimate)

February 19, 2014

Study Record Updates

Last Update Posted (Actual)

July 30, 2021

Last Update Submitted That Met QC Criteria

July 28, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M13-537
  • 2013-003984-72 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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