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Rheumatoid ArthritisPhase 2NCT02066389

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

A Phase 2 study testing Upadacitinib in people with Rheumatoid Arthritis, run by AbbVie at 63 sites in 16 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Upadacitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
300 participants
Where
63 sitesin 16 countries
Study dates
26 Mar 2014to 2 Jul 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • 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.
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  • 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)
  • 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.
  • 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.
  • 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.

Who cannot join

  • Female who is pregnant or breastfeeding.
  • Prior exposure to Janus activated kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib).
  • Prior exposure to any investigational or approved biologic RA therapy.
  • 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.
  • 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).
  • Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 8 weeks prior to the Week 0 Visit.
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  • 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

Trial locations and contacts

63 sites in 16 countries.

63 sites in 16 countries

United States12 sites

  • Mountain State Clinical Resear /ID# 127089

    Clarksburg, West Virginia, 26301

  • Summit Medical Group /ID# 125776

    Clifton, New Jersey, 07012

  • Omega Research Consultants, LLC /ID# 125780

    DeBary, Florida, 32713-2260

  • Altoona Ctr Clinical Res /ID# 125777

    Duncansville, Pennsylvania, 16635

  • C.V. Mehta MD, Med Corporation /ID# 126380

    Hemet, California, 92543

  • Accurate Clinical Research /ID# 126535

    Houston, Texas, 77034

  • Arthritis and Osteo Assoc /ID# 134994

    Las Cruces, New Mexico, 88011

  • North Georgia Rheumatology Grp /ID# 125779

    Lawrenceville, Georgia, 30045

  • Lovelace Scientific Resources /ID# 127324

    Venice, Florida, 34292

  • The Center for Rheumatology & /ID# 127323

    Wheaton, Maryland, 20902

  • PRN Professional Research Network of Kansas, LLC /ID# 126148

    Wichita, Kansas, 67205

  • Emkey Arthritis and Osteo Clin /ID# 134716

    Wyomissing, Pennsylvania, 19610

Other trials in United States

Spain8 sites

  • Hospital Plató /ID# 127384

    Barcelona, 08006

  • Hospital CIMA Sanitas /ID# 127383

    Barcelona, 08034

  • Hospital Universitario Basurto /ID# 127391

    Bilbao, 48013

  • Hospital Clin Univ San Carlos /ID# 127382

    Madrid, 28040

  • Hospital Regional de Malaga /ID# 127385

    Málaga, Malaga, 29009

  • Clinica Gaias /ID# 127386

    Santiago de Compostela, 15702

  • Hospital Infanta Luisa /ID# 127389

    Seville, 41010

  • Hospital Universitario de Valm /ID# 127387

    Seville, 41014

Other trials in Spain

Bulgaria7 sites

  • MHAT Trimontsium /ID# 127311

    Plovdiv, 4000

  • UMHAT Pulmed OOD /ID# 127307

    Plovdiv, 4000

  • MHAT Kaspela /ID# 127315

    Plovdiv, 4001

  • Diagnostic Consultative Center /ID# 127313

    Sofia, 1612

  • UMHAT Sv. Ivan Rilski /ID# 127314

    Sofia, 1612

  • UMHAT Sv. Ivan Rilski /ID# 131608

    Sofia, 1612

  • Diagnostic Consultative Center /ID# 127312

    Varna, 9000

Other trials in Bulgaria

Poland7 sites

  • Gabinet Internistyczno Reum. /ID# 127357

    Bialystok, Podlaskie Voivodeship, 15-099

  • Michal Bazela Higher-Med /ID# 127355

    Elblag, Warmian-Masurian Voivodeship, 82-300

  • Centrum Medyczne Pratia Gdynia /ID# 127360

    Gdynia, Pomeranian Voivodeship, 81-338

  • Centrum Medyczne Pratia Krakow /ID# 127358

    Krakow, Lesser Poland Voivodeship, 30-002

  • REUMED Sp.z o.o. Filia nr 1 /ID# 127353

    Lublin, Lublin Voivodeship, 20-607

  • NBR Polska /ID# 127359

    Warsaw, Masovian Voivodeship, 00-465

  • Medica Pro Familia S.A Warszawa /ID# 127361

    Warsaw, Masovian Voivodeship, 01-869

Other trials in Poland

Czechia4 sites

  • Revmatologie Bruntal, s.r.o /ID# 126881

    Bruntál, 79201

  • Artroscan s.r.o. /ID# 126845

    Ostrava, 722 00

  • Revmatologicky ustav Praha /ID# 127317

    Prague, Praha 2, 128 00

  • Nuselská poliklinika, Revmatologie /ID# 127318

    Prague, Praha 4, 140 00

Other trials in Czechia

Israel3 sites

  • Barzilai Medical Center /ID# 126875

    Ashkelon, 78278

  • Rambam Health Care Campus /ID# 127341

    Haifa, 3109601

  • Sheba Medical Center /ID# 126878

    Ramat Gan, 5262100

Other trials in Israel

Latvia3 sites

  • LTD M&M Centers /ID# 127346

    Adazi, 2164

  • Arija's Ancane's Family Doctor /ID# 127342

    Baldone, 2125

  • Clinic ORTO /ID# 127345

    Riga, 1005

Other trials in Latvia

Mexico3 sites

  • Hospital de Jesús Nazareno /ID# 127352

    Mexico City, 06090

  • Cliditer SA de CV /ID# 127347

    Mexico City, 06700

  • Clinstile, S.A. de C.V. /ID# 127350

    Mexico City, 06700

Other trials in Mexico

Russia3 sites

  • City Clinical Hospital #7 /ID# 127372

    Kazan', Tatarstan, Respublika, 420103

  • II Dzhan Research Center /ID# 127376

    Saint Petersburg, 192242

  • Tver Regional Clinical Hosp. /ID# 127375

    Tver', Tver Oblast, 170036

Other trials in Russia

Ukraine3 sites

  • Kiev Municipal Clin Hosp 3 /ID# 127419

    Kiev, 02125

  • NSC-Strazhesko Ist Cardiology /ID# 127416

    Kiev, 03680

  • Sumy State University /ID# 127418

    Sumy, 40000

Other trials in Ukraine

Chile2 sites

  • Corp de Beneficencia Osorno /ID# 127337

    Osorno, 1710216

  • Quantum Research LTDA. /ID# 127338

    Puerto Varas, 5550170

Other trials in Chile

Hungary2 sites

  • Qualiclinic Kft. /ID# 127340

    Budapest III, Pest County, 1036

  • Veszprem Megyei Csolnoky Feren /ID# 126876

    Veszprém, 8200

Other trials in Hungary

Slovakia2 sites

  • MEDMAN s.r.o. /ID# 127381

    Martin, 036 01

  • Poliklinika Senica /ID# 127396

    Senica, 905 01

Other trials in Slovakia

South Africa2 sites

  • Panorama Medical Centre /ID# 126846

    Cape Town, Western Cape, 7500

  • Winelands Medical Research Ctr /ID# 126844

    Stellenbosch, Western Cape, 7600

Other trials in South Africa

Puerto Rico1 site

  • GCM Medical Group /ID# 127363

    San Juan, 00909

Other trials in Puerto Rico

Turkey (Türkiye)1 site

  • Medeniyet Univ. Goztepe Traini /ID# 132396

    Istanbul, 34000

Other trials in Turkey (Türkiye)

About this study

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

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.

Being tested
Placebo, Upadacitinib
Keywords
Musculoskeletal Disease, Arthritis, Joint Diseases, anti-inflammatory agents, antirheumatic agents
Medical subject headings
Arthritis, Rheumatoid, Musculoskeletal Diseases, Arthritis, Joint Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Tablets for oral administration

  • UpadacitinibDrug

    Also called ABT-494

    Tablets for oral administration

Study groups in NCT02066389
Study groupRoleWhat they receive
PlaceboPlacebo comparatorParticipants received placebo capsules twice daily for 12 weeks.
Receives: Drug: Placebo
Upadacitinib 3 mg BIDExperimentalParticipants received 3 mg upadacitinib twice daily (BID) for 12 weeks.
Receives: Drug: Upadacitinib
Upadacitinib 6 mg BIDExperimentalParticipants received 6 mg upadacitinib twice daily (BID) for 12 weeks.
Receives: Drug: Upadacitinib
Upadacitinib 12 mg BIDExperimentalParticipants received 12 mg upadacitinib twice daily (BID) for 12 weeks.
Receives: Drug: Upadacitinib
Upadacitinib 18 mg BIDExperimentalParticipants received 18 mg upadacitinib twice daily (BID) for 12 weeks.
Receives: Drug: Upadacitinib
Upadacitinib 24 mg QDExperimentalParticipants received 24 mg upadacitinib once daily (QD) for 12 weeks.
Receives: Drug: Upadacitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response 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).

    Measured: Baseline and Week 12

Secondary outcomes (6)

  1. Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at 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).

    Measured: Baseline and Week 12

  2. Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at 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).

    Measured: Baseline and Week 12

  3. Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at 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.

    Measured: Week 12

  4. Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at 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.

    Measured: Week 12

  5. Percentage of Participants Achieving Low Disease Activity (LDA) Based on CDAI at 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.

    Measured: Week 12

  6. Percentage of Participants Achieving Clinical Remission Based on CDAI at 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.

    Measured: Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2014 (estimated)
  2. Study start26 Mar 2014
  3. Primary completion2 Jul 2015
  4. Study completion2 Jul 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
300 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02066389
Sponsor's protocol ID
M13-537
Other IDs
2013-003984-72
Status last verified
Jul 2021
First submitted
17 Feb 2014
Last updated
30 Jul 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Genovese MC, Smolen JS, Weinblatt ME, Burmester GR, Meerwein S, Camp HS, Wang L, Othman AA, Khan N, Pangan AL, Jungerwirth S. Efficacy and Safety of ABT-494, a Selective JAK-1 Inhibitor, in a Phase IIb Study in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate. Arthritis Rheumatol. 2016 Dec;68(12):2857-2866. doi: 10.1002/art.39808.

    PubMed 27390150

  • Yamaoka K, Tanaka Y, Kameda H, Khan N, Sasaki N, Harigai M, Song Y, Zhang Y, Takeuchi T. The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan. Drug Saf. 2021 Jun;44(6):711-722. doi: 10.1007/s40264-021-01067-x. Epub 2021 May 27.

    PubMed 34041702

  • Nader A, Mohamed MF, Winzenborg I, Doelger E, Noertersheuser P, Pangan AL, Othman AA. Exposure-Response Analyses of Upadacitinib Efficacy and Safety in Phase II and III Studies to Support Benefit-Risk Assessment in Rheumatoid Arthritis. Clin Pharmacol Ther. 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671. Epub 2019 Nov 30.

    PubMed 31610021

  • Mohamed MF, Klunder B, Camp HS, Othman AA. Exposure-Response Analyses of Upadacitinib Efficacy in Phase II Trials in Rheumatoid Arthritis and Basis for Phase III Dose Selection. Clin Pharmacol Ther. 2019 Dec;106(6):1319-1327. doi: 10.1002/cpt.1543. Epub 2019 Aug 23.

    PubMed 31194885

  • Klunder B, Mohamed MF, Othman AA. Population Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects with Rheumatoid Arthritis: Analyses of Phase I and II Clinical Trials. Clin Pharmacokinet. 2018 Aug;57(8):977-988. doi: 10.1007/s40262-017-0605-6.

    PubMed 29076110

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Upadacitinib in people with Rheumatoid Arthritis, run by AbbVie at 63 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 63 sites in United States, Spain, Bulgaria, Poland, Czechia and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02066389, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2021.

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