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

NCT ID: NCT02066389

Last Updated: 2021-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-26
• Study Completion Date: 2015-07-02

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Participants received placebo capsules twice daily for 12 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablets for oral administration

Upadacitinib 3 mg BID

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

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablets for oral administration

Upadacitinib 6 mg BID

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

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablets for oral administration

Upadacitinib 12 mg BID

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

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablets for oral administration

Upadacitinib 18 mg BID

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

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablets for oral administration

Upadacitinib 24 mg QD

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

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablets for oral administration

Interventions

Placebo

Tablets for oral administration

Intervention Type: DRUG

Upadacitinib

Tablets for oral administration

Intervention Type: DRUG

Other Intervention Names

ABT-494

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

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

Hemet, California, United States

Omega Research Consultants, LLC /ID# 125780

DeBary, Florida, United States

Lovelace Scientific Resources /ID# 127324

Venice, Florida, United States

North Georgia Rheumatology Grp /ID# 125779

Lawrenceville, Georgia, United States

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

Wichita, Kansas, United States

The Center for Rheumatology & /ID# 127323

Wheaton, Maryland, United States

Summit Medical Group /ID# 125776

Clifton, New Jersey, United States

Arthritis and Osteo Assoc /ID# 134994

Las Cruces, New Mexico, United States

Altoona Ctr Clinical Res /ID# 125777

Duncansville, Pennsylvania, United States

Emkey Arthritis and Osteo Clin /ID# 134716

Wyomissing, Pennsylvania, United States

Accurate Clinical Research /ID# 126535

Houston, Texas, United States

Mountain State Clinical Resear /ID# 127089

Clarksburg, West Virginia, United States

MHAT Trimontsium /ID# 127311

Plovdiv, , Bulgaria

UMHAT Pulmed OOD /ID# 127307

Plovdiv, , Bulgaria

MHAT Kaspela /ID# 127315

Plovdiv, , Bulgaria

Diagnostic Consultative Center /ID# 127313

Sofia, , Bulgaria

UMHAT Sv. Ivan Rilski /ID# 127314

Sofia, , Bulgaria

UMHAT Sv. Ivan Rilski /ID# 131608

Sofia, , Bulgaria

Diagnostic Consultative Center /ID# 127312

Varna, , Bulgaria

Corp de Beneficencia Osorno /ID# 127337

Osorno, , Chile

Quantum Research LTDA. /ID# 127338

Puerto Varas, , Chile

Revmatologicky ustav Praha /ID# 127317

Prague, Praha 2, Czechia

Nuselská poliklinika, Revmatologie /ID# 127318

Prague, Praha 4, Czechia

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

Bruntál, , Czechia

Artroscan s.r.o. /ID# 126845

Ostrava, , Czechia

Qualiclinic Kft. /ID# 127340

Budapest III, Pest County, Hungary

Veszprem Megyei Csolnoky Feren /ID# 126876

Veszprém, , Hungary

Barzilai Medical Center /ID# 126875

Ashkelon, , Israel

Rambam Health Care Campus /ID# 127341

Haifa, , Israel

Sheba Medical Center /ID# 126878

Ramat Gan, , Israel

LTD M&M Centers /ID# 127346

Ādaži, , Latvia

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

Baldone, , Latvia

Clinic ORTO /ID# 127345

Riga, , Latvia

Hospital de Jesús Nazareno /ID# 127352

Mexico City, , Mexico

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, Lesser Poland Voivodeship, Poland

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

Lublin, Lublin Voivodeship, Poland

NBR Polska /ID# 127359

Warsaw, Masovian Voivodeship, Poland

Medica Pro Familia S.A Warszawa /ID# 127361

Warsaw, Masovian Voivodeship, Poland

Gabinet Internistyczno Reum. /ID# 127357

Bialystok, Podlaskie Voivodeship, Poland

Centrum Medyczne Pratia Gdynia /ID# 127360

Gdynia, Pomeranian Voivodeship, Poland

Michal Bazela Higher-Med /ID# 127355

Elblag, Warmian-Masurian Voivodeship, Poland

GCM Medical Group /ID# 127363

San Juan, , Puerto Rico

City Clinical Hospital #7 /ID# 127372

Kazan', Tatarstan, Respublika, Russia

Tver Regional Clinical Hosp. /ID# 127375

Tver', Tver Oblast, Russia

II Dzhan Research Center /ID# 127376

Saint Petersburg, , Russia

MEDMAN s.r.o. /ID# 127381

Martin, , Slovakia

Poliklinika Senica /ID# 127396

Senica, , Slovakia

Panorama Medical Centre /ID# 126846

Cape Town, Western Cape, South Africa

Winelands Medical Research Ctr /ID# 126844

Stellenbosch, Western Cape, South Africa

Hospital Regional de Malaga /ID# 127385

Málaga, Malaga, Spain

Hospital Plató /ID# 127384

Barcelona, , Spain

Hospital CIMA Sanitas /ID# 127383

Barcelona, , Spain

Hospital Universitario Basurto /ID# 127391

Bilbao, , Spain

Hospital Clin Univ San Carlos /ID# 127382

Madrid, , Spain

Clinica Gaias /ID# 127386

Santiago de Compostela, , Spain

Hospital Infanta Luisa /ID# 127389

Seville, , Spain

Hospital Universitario de Valm /ID# 127387

Seville, , Spain

Medeniyet Univ. Goztepe Traini /ID# 132396

Istanbul, , Turkey (Türkiye)

Kiev Municipal Clin Hosp 3 /ID# 127419

Kiev, , Ukraine

NSC-Strazhesko Ist Cardiology /ID# 127416

Kiev, , Ukraine

Sumy State University /ID# 127418

Sumy, , Ukraine

Countries

United States; Bulgaria; Chile; Czechia; Hungary; Israel; Latvia; Mexico; Poland; Puerto Rico; Russia; Slovakia; South Africa; Spain; Turkey (Türkiye); Ukraine

References

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.

Reference Type: BACKGROUND

PMID: 27390150 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34041702 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31610021 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31194885 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29076110 (View on PubMed)

Other Identifiers

2013-003984-72

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M13-537

Identifier Type: -

Identifier Source: org_study_id