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
- Registration Number
- NCT02066389
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 300
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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.
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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.
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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)
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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.
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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.
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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.
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Female who is pregnant or breastfeeding.
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Prior exposure to Janus activated kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib).
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Prior exposure to any investigational or approved biologic RA therapy.
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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.
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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).
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received placebo capsules twice daily for 12 weeks. Upadacitinib 3 mg BID Upadacitinib Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks. Upadacitinib 12 mg BID Upadacitinib Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks. Upadacitinib 6 mg BID Upadacitinib Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks. Upadacitinib 18 mg BID Upadacitinib Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks. Upadacitinib 24 mg QD Upadacitinib Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 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
Name Time Method Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12 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.Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 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.Percentage of Participants Achieving Clinical Remission Based on CDAI at Week 12 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.Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 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).Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 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).Percentage of Participants Achieving Low Disease Activity (LDA) Based on CDAI at Week 12 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.
Trial Locations
- Locations (63)
C.V. Mehta MD, Med Corporation /ID# 126380
🇺🇸Hemet, California, United States
Mountain State Clinical Resear /ID# 127089
🇺🇸Clarksburg, West Virginia, United States
Panorama Medical Centre /ID# 126846
🇿🇦Cape Town, Western Cape, South Africa
UMHAT Pulmed OOD /ID# 127307
🇧🇬Plovdiv, Bulgaria
Omega Research Consultants, LLC /ID# 125780
🇺🇸DeBary, Florida, United States
LTD M&M Centers /ID# 127346
🇱🇻Adazi, Latvia
Diagnostic Consultative Center /ID# 127313
🇧🇬Sofia, Bulgaria
Diagnostic Consultative Center /ID# 127312
🇧🇬Varna, Bulgaria
Clinic ORTO /ID# 127345
🇱🇻Riga, Latvia
Hospital de Jesús Nazareno /ID# 127352
🇲🇽Mexico City, Mexico
Veszprem Megyei Csolnoky Feren /ID# 126876
🇭🇺Veszprém, Hungary
MHAT Kaspela /ID# 127315
🇧🇬Plovdiv, Bulgaria
North Georgia Rheumatology Grp /ID# 125779
🇺🇸Lawrenceville, Georgia, United States
Lovelace Scientific Resources /ID# 127324
🇺🇸Venice, Florida, United States
PRN Professional Research Network of Kansas, LLC /ID# 126148
🇺🇸Wichita, Kansas, United States
Arthritis and Osteo Assoc /ID# 134994
🇺🇸Las Cruces, New Mexico, United States
The Center for Rheumatology & /ID# 127323
🇺🇸Wheaton, Maryland, United States
Summit Medical Group /ID# 125776
🇺🇸Clifton, New Jersey, United States
Altoona Ctr Clinical Res /ID# 125777
🇺🇸Duncansville, Pennsylvania, United States
MHAT Trimontsium /ID# 127311
🇧🇬Plovdiv, Bulgaria
Accurate Clinical Research /ID# 126535
🇺🇸Houston, Texas, United States
Emkey Arthritis and Osteo Clin /ID# 134716
🇺🇸Wyomissing, Pennsylvania, United States
UMHAT Sv. Ivan Rilski /ID# 127314
🇧🇬Sofia, Bulgaria
UMHAT Sv. Ivan Rilski /ID# 131608
🇧🇬Sofia, Bulgaria
Quantum Research LTDA. /ID# 127338
🇨🇱Puerto Varas, Chile
Corp de Beneficencia Osorno /ID# 127337
🇨🇱Osorno, Chile
Qualiclinic Kft. /ID# 127340
🇭🇺Budapest III, Pest, Hungary
Nuselská poliklinika, Revmatologie /ID# 127318
🇨🇿Prague 4, Praha 4, Czechia
Revmatologicky ustav Praha /ID# 127317
🇨🇿Prague 2, Praha 2, Czechia
Revmatologie Bruntal, s.r.o /ID# 126881
🇨🇿Bruntál, Czechia
Rambam Health Care Campus /ID# 127341
🇮🇱Haifa, Israel
Barzilai Medical Center /ID# 126875
🇮🇱Ashkelon, Israel
Artroscan s.r.o. /ID# 126845
🇨🇿Ostrava, Czechia
Sheba Medical Center /ID# 126878
🇮🇱Ramat Gan, Israel
Arija's Ancane's Family Doctor /ID# 127342
🇱🇻Baldone, Latvia
Cliditer SA de CV /ID# 127347
🇲🇽Mexico City, Mexico
Clinstile, S.A. de C.V. /ID# 127350
🇲🇽Mexico City, Mexico
Centrum Medyczne Pratia Krakow /ID# 127358
🇵🇱Krakow, Malopolskie, Poland
NBR Polska /ID# 127359
🇵🇱Warsaw, Mazowieckie, Poland
REUMED Sp.z o.o. Filia nr 1 /ID# 127353
🇵🇱Lublin, Lubelskie, Poland
Medica Pro Familia S.A Warszawa /ID# 127361
🇵🇱Warsaw, Mazowieckie, Poland
Centrum Medyczne Pratia Gdynia /ID# 127360
🇵🇱Gdynia, Pomorskie, Poland
Gabinet Internistyczno Reum. /ID# 127357
🇵🇱Białystok, Podlaskie, Poland
Michal Bazela Higher-Med /ID# 127355
🇵🇱Elbląg, Warminsko-mazurskie, Poland
GCM Medical Group /ID# 127363
🇵🇷San Juan, Puerto Rico
City Clinical Hospital #7 /ID# 127372
🇷🇺Kazan, Tatarstan, Respublika, Russian Federation
Tver Regional Clinical Hosp. /ID# 127375
🇷🇺Tver, Tverskaya Oblast, Russian Federation
II Dzhan Research Center /ID# 127376
🇷🇺St. Petersburg, Russian Federation
MEDMAN s.r.o. /ID# 127381
🇸🇰Martin, Slovakia
Poliklinika Senica /ID# 127396
🇸🇰Senica, Slovakia
Winelands Medical Research Ctr /ID# 126844
🇿🇦Stellenbosch, Western Cape, South Africa
Hospital CIMA Sanitas /ID# 127383
🇪🇸Barcelona, Spain
Hospital Regional de Malaga /ID# 127385
🇪🇸Málaga, Malaga, Spain
Hospital Universitario de Valm /ID# 127387
🇪🇸Sevilla, Spain
Hospital Plató /ID# 127384
🇪🇸Barcelona, Spain
Hospital Universitario Basurto /ID# 127391
🇪🇸Bilbao, Spain
Clinica Gaias /ID# 127386
🇪🇸Santiago de Compostela, Spain
Medeniyet Univ. Goztepe Traini /ID# 132396
🇹🇷Istanbul, Turkey
NSC-Strazhesko Ist Cardiology /ID# 127416
🇺🇦Kiev, Ukraine
Sumy State University /ID# 127418
🇺🇦Sumy, Ukraine
Hospital Infanta Luisa /ID# 127389
🇪🇸Sevilla, Spain
Kiev Municipal Clin Hosp 3 /ID# 127419
🇺🇦Kiev, Ukraine
Hospital Clin Univ San Carlos /ID# 127382
🇪🇸Madrid, Spain