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

NCT02066389 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: M13-5372013-003984-72
• Study Type: interventional
• Target: 300
• Locations: 16 countries
• Sites: 63

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.

Conditions

Rheumatoid Arthritis

Keywords

Musculoskeletal Disease; Arthritis; Joint Diseases; anti-inflammatory agents; antirheumatic agents

Outcome Measures

Primary Outcomes (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).

  Baseline and Week 12

Secondary Outcomes (6)

• Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12

  Baseline and Week 12

• Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12

  Baseline and Week 12

• Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12

  Week 12

• Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12

  Week 12

• Percentage of Participants Achieving Low Disease Activity (LDA) Based on CDAI at Week 12

  Week 12

Study Arms (6)

Placebo

PLACEBO COMPARATOR

Participants received placebo capsules twice daily for 12 weeks.

Drug: Placebo

Upadacitinib 3 mg BID

EXPERIMENTAL

Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.

Drug: Upadacitinib

Upadacitinib 6 mg BID

EXPERIMENTAL

Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.

Drug: Upadacitinib

Upadacitinib 12 mg BID

EXPERIMENTAL

Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.

Drug: Upadacitinib

Upadacitinib 18 mg BID

EXPERIMENTAL

Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.

Drug: Upadacitinib

Upadacitinib 24 mg QD

EXPERIMENTAL

Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.

Drug: Upadacitinib

Interventions

Placebo DRUG

Tablets for oral administration

Placebo

Upadacitinib DRUG

Tablets for oral administration

Also known as: ABT-494

Upadacitinib 12 mg BID; Upadacitinib 18 mg BID; Upadacitinib 24 mg QD; Upadacitinib 3 mg BID; Upadacitinib 6 mg BID

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 8 weeks prior to the Week 0 Visit.
• 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

Sponsors & Collaborators

• AbbVie: lead

Study Sites (63)

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

Hemet, California, 92543, United States

Location

Omega Research Consultants, LLC /ID# 125780

DeBary, Florida, 32713-2260, United States

Location

Lovelace Scientific Resources /ID# 127324

Venice, Florida, 34292, United States

Location

North Georgia Rheumatology Grp /ID# 125779

Lawrenceville, Georgia, 30045, United States

Location

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

Wichita, Kansas, 67205, United States

Location

The Center for Rheumatology & /ID# 127323

Wheaton, Maryland, 20902, United States

Location

Summit Medical Group /ID# 125776

Clifton, New Jersey, 07012, United States

Location

Arthritis and Osteo Assoc /ID# 134994

Las Cruces, New Mexico, 88011, United States

Location

Altoona Ctr Clinical Res /ID# 125777

Duncansville, Pennsylvania, 16635, United States

Location

Emkey Arthritis and Osteo Clin /ID# 134716

Wyomissing, Pennsylvania, 19610, United States

Location

Accurate Clinical Research /ID# 126535

Houston, Texas, 77034, United States

Location

Mountain State Clinical Resear /ID# 127089

Clarksburg, West Virginia, 26301, United States

Location

MHAT Trimontsium /ID# 127311

Plovdiv, 4000, Bulgaria

Location

UMHAT Pulmed OOD /ID# 127307

Plovdiv, 4000, Bulgaria

Location

MHAT Kaspela /ID# 127315

Plovdiv, 4001, Bulgaria

Location

Diagnostic Consultative Center /ID# 127313

Sofia, 1612, Bulgaria

Location

UMHAT Sv. Ivan Rilski /ID# 127314

Sofia, 1612, Bulgaria

Location

UMHAT Sv. Ivan Rilski /ID# 131608

Sofia, 1612, Bulgaria

Location

Diagnostic Consultative Center /ID# 127312

Varna, 9000, Bulgaria

Location

Corp de Beneficencia Osorno /ID# 127337

Osorno, 1710216, Chile

Location

Quantum Research LTDA. /ID# 127338

Puerto Varas, 5550170, Chile

Location

Revmatologicky ustav Praha /ID# 127317

Prague, Praha 2, 128 00, Czechia

Location

Nuselská poliklinika, Revmatologie /ID# 127318

Prague, Praha 4, 140 00, Czechia

Location

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

Bruntál, 79201, Czechia

Location

Artroscan s.r.o. /ID# 126845

Ostrava, 722 00, Czechia

Location

Qualiclinic Kft. /ID# 127340

Budapest III, Pest County, 1036, Hungary

Location

Veszprem Megyei Csolnoky Feren /ID# 126876

Veszprém, 8200, Hungary

Location

Barzilai Medical Center /ID# 126875

Ashkelon, 78278, Israel

Location

Rambam Health Care Campus /ID# 127341

Haifa, 3109601, Israel

Location

Sheba Medical Center /ID# 126878

Ramat Gan, 5262100, Israel

Location

LTD M&M Centers /ID# 127346

Ādaži, 2164, Latvia

Location

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

Baldone, 2125, Latvia

Location

Clinic ORTO /ID# 127345

Riga, 1005, Latvia

Location

Hospital de Jesús Nazareno /ID# 127352

Mexico City, 06090, Mexico

Location

Cliditer SA de CV /ID# 127347

Mexico City, 06700, Mexico

Location

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

Mexico City, 06700, Mexico

Location

Centrum Medyczne Pratia Krakow /ID# 127358

Krakow, Lesser Poland Voivodeship, 30-002, Poland

Location

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

Lublin, Lublin Voivodeship, 20-607, Poland

Location

NBR Polska /ID# 127359

Warsaw, Masovian Voivodeship, 00-465, Poland

Location

Medica Pro Familia S.A Warszawa /ID# 127361

Warsaw, Masovian Voivodeship, 01-869, Poland

Location

Gabinet Internistyczno Reum. /ID# 127357

Bialystok, Podlaskie Voivodeship, 15-099, Poland

Location

Centrum Medyczne Pratia Gdynia /ID# 127360

Gdynia, Pomeranian Voivodeship, 81-338, Poland

Location

Michal Bazela Higher-Med /ID# 127355

Elblag, Warmian-Masurian Voivodeship, 82-300, Poland

Location

GCM Medical Group /ID# 127363

San Juan, 00909, Puerto Rico

Location

City Clinical Hospital #7 /ID# 127372

Kazan', Tatarstan, Respublika, 420103, Russia

Location

Tver Regional Clinical Hosp. /ID# 127375

Tver', Tver Oblast, 170036, Russia

Location

II Dzhan Research Center /ID# 127376

Saint Petersburg, 192242, Russia

Location

MEDMAN s.r.o. /ID# 127381

Martin, 036 01, Slovakia

Location

Poliklinika Senica /ID# 127396

Senica, 905 01, Slovakia

Location

Panorama Medical Centre /ID# 126846

Cape Town, Western Cape, 7500, South Africa

Location

Winelands Medical Research Ctr /ID# 126844

Stellenbosch, Western Cape, 7600, South Africa

Location

Hospital Regional de Malaga /ID# 127385

Málaga, Malaga, 29009, Spain

Location

Hospital Plató /ID# 127384

Barcelona, 08006, Spain

Location

Hospital CIMA Sanitas /ID# 127383

Barcelona, 08034, Spain

Location

Hospital Universitario Basurto /ID# 127391

Bilbao, 48013, Spain

Location

Hospital Clin Univ San Carlos /ID# 127382

Madrid, 28040, Spain

Location

Clinica Gaias /ID# 127386

Santiago de Compostela, 15702, Spain

Location

Hospital Infanta Luisa /ID# 127389

Seville, 41010, Spain

Location

Hospital Universitario de Valm /ID# 127387

Seville, 41014, Spain

Location

Medeniyet Univ. Goztepe Traini /ID# 132396

Istanbul, 34000, Turkey (Türkiye)

Location

Kiev Municipal Clin Hosp 3 /ID# 127419

Kiev, 02125, Ukraine

Location

NSC-Strazhesko Ist Cardiology /ID# 127416

Kiev, 03680, Ukraine

Location

Sumy State University /ID# 127418

Sumy, 40000, Ukraine

Location

Related Publications (5)

• 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.

  PMID: 27390150 BACKGROUND

• 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.

  PMID: 34041702 DERIVED

• 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.

  PMID: 31610021 DERIVED

• 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.

  PMID: 31194885 DERIVED

• 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.

  PMID: 29076110 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid; Musculoskeletal Diseases; Arthritis; Joint Diseases

Interventions

upadacitinib

Condition Hierarchy (Ancestors)

Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2014
• First Posted: February 19, 2014
• Study Start: March 26, 2014
• Primary Completion: July 2, 2015
• Study Completion: July 2, 2015
• Last Updated: July 30, 2021
• Results First Posted: October 4, 2019

Record last verified: 2021-07

Locations

ME (3); LA (3); RU (3); ES (8); PR (1); CZ (4); TU (1); PL (7); US (12); ZA (2); CL (2); BU (7); IL (3); UA (3); SL (2); HU (2)