An Open-label Extension Study Evaluating the Safety and Efficacy of Upadacitinib (ABT-494) in Adults With Rheumatoid Arthritis

NCT ID: NCT02049138

Last Updated: 2022-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 493 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-24
• Study Completion Date: 2021-07-29

Brief Summary

The primary objective of the study is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib in adults with rheumatoid arthritis (RA) who have completed a preceding randomized controlled trial with upadacitinib.

Detailed Description

This is an open-label extension study to assess the long-term safety, tolerability, and efficacy of upadacitinib in adults with RA who have completed Study M13-550 (NCT01960855) or Study M13-537 (NCT02066389) Phase 2 randomized controlled trial (RCT) with upadacitinib.

All participants received treatment with 6 mg upadacitinib twice a day at the start of the study. Participants may have been up-titrated to 12 mg BID based on protocol-specified criteria. In Protocol Amendment 2 (January 2016) the study treatment was changed to a once daily (QD) formulation. Participants receiving 6 mg BID were transitioned to 15 mg QD and participants receiving 12 mg BID were transitioned to 30 mg QD dosing.

An optional 12-week vaccine sub-study was added in Protocol Amendment 3 (November 2017) to assess the impact of upadacitinib treatment (15 mg QD and 30 mg QD) with background methotrexate on immunological responses to pneumococcal 13-valent conjugate vaccine (PCV-13; Prevnar 13®) in RA patients. The vaccine substudy included 111 participants who were enrolled in the main study, the first participant was enrolled on 13 February 2018 and the the last participant completed the sub-study on 9 April 2020.

In Protocol Amendment 5 (December 2019), the protocol was revised to allow a decrease in upadacitinib dosing from 30 mg QD to 15 mg QD, as appropriate, based on investigator's medical decision or for safety/tolerability concerns.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Upadacitinib

Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). Participants who did not achieve a 20% improvement from RCT Baseline in both Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 6 or Week 12 were up-titrated to 12 mg BID. From January 2017 participants were transitioned to a once-daily (QD) regimen of upadacitinib, either 15 mg QD (participants who were taking 6 mg BID) or 30 mg QD (participants taking 12 mg BID). Starting with Protocol Amendment 5 participants receiving 30 mg QD upadacitinib had the option to decrease the dose to 15 mg QD at the investigator's discretion.

A subset of participants who opted-in to the vaccine substudy received a single-dose of 0.5 mL intramuscular injection of pneumococcal 13-valent conjugate vaccine (PCV-13).

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablet taken orally

Pneumococcal 13-valent conjugate vaccine (PCV-13)

Intervention Type: BIOLOGICAL

Administered by intramuscular injection

Interventions

Upadacitinib

Tablet taken orally

Intervention Type: DRUG

Pneumococcal 13-valent conjugate vaccine (PCV-13)

Administered by intramuscular injection

Intervention Type: BIOLOGICAL

Other Intervention Names

ABT-494; RINVOQ®; Prevnar 13®

Eligibility Criteria

Inclusion Criteria

1. Subjects who have completed Study M13-550 (NCT01960855) or Study M13-537 (NCT02066389) with upadacitinib (ABT-494) and did not develop any discontinuation criteria.

2. If the subject has evidence of new latent tuberculosis (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 before continuing to receive study drug.

3. If female, subject must be postmenopausal, OR permanently surgically sterile, OR for women of childbearing potential practicing at least one protocol-specified method of birth control, that is effective from Study Day 1 through at least 30 days after the last dose of study drug.

4. Subjects must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.

Substudy:

1. Must currently be enrolled in the main study.

2. Must have been receiving a stable dose of upadacitinib (either 15 mg QD or 30 mg QD) for a minimum of 4 weeks prior to the Vaccination visit.

3. Must have been on a stable dose of background methotrexate (no change in dose or frequency) for a minimum of 4 weeks prior to the Vaccination visit.

4. If subject is on corticosteroids, must remain on a stable dose of ≤ 10 mg/day of prednisone or equivalent corticosteroid therapy for at least 4 weeks after the vaccination visit.

5. Must meet the prescribing specifications as per local label requirements to receive Prevnar 13® vaccine.

6. Willing to receive Prevnar13® vaccine.

Exclusion Criteria

1. Pregnant or breastfeeding female.

2. Ongoing infections at Week 0 that have not been successfully treated. Subjects with ongoing infections undergoing treatment may be enrolled but not dosed until the infection has been successfully treated.

3. Anticipated requirement or receipt of any live vaccine during study participation including up to 30 days after the last dose of study drug.

4. Laboratory values from the visit immediately prior to Baseline Visit (local requirements may apply) meeting the following criteria:

• Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 3.0 × upper limit of normal (ULN)
• Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73m^2
• Total white blood cell count (WBC) < 2,000/μL
• Absolute neutrophil count (ANC) < 1,000/μL
• Platelet count < 50,000/μL
• Absolute lymphocytes count < 500/μL
• Hemoglobin < 8 g/dL

5. Enrollment in another interventional clinical study while participating in this study.

6. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive study drug.

Substudy:

1. Receiving any conventional synthetic disease modifying antirheumatic drugs (csDMARDs) other than methotrexate

2. Receiving > 10 mg/day of prednisone or equivalent corticosteroid therapy.

3. Receipt of any steroid injection within 4 weeks prior to Vaccination visit.

4. History of severe allergic reaction (e.g., anaphylaxis) to any component of Prevnar 13®.

5. History of any documented pneumococcal infection within the last 6 months prior to the vaccination visit.

6. Receipt of any vaccine 4 weeks prior to the vaccination visit and/or anticipation of any vaccination for 4 weeks after the vaccination visit.

7. Receipt of any pneumococcal vaccine.

8. Subject is not suitable for the sub-study as per the Investigator's judgment.

• 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

Rheum Assoc of North Alabama /ID# 135926

Huntsville, Alabama, United States

AZ Arthritis and Rheumotology Research, PLLC /ID# 135902

Phoenix, Arizona, United States

AZ Arthritis and Rheumotology Research, PLLC /ID# 135931

Phoenix, Arizona, United States

C.V. Mehta MD, Med Corporation /ID# 124092

Hemet, California, United States

Moores Cancer Center at UC San Diego /ID# 128747

La Jolla, California, United States

Desert Medical Advances - Palm Desert /ID# 135911

Palm Desert, California, United States

Orrin Troum, M.D. and Medical /ID# 135933

Santa Monica, California, United States

Duplicate_Robin K. Dore MD, Inc /ID# 135906

Tustin, California, United States

Inland Rheum Clin Trials Inc. /ID# 136716

Upland, California, United States

Duplicate_Desert Valley Medical Group /ID# 135932

Victorville, California, United States

Denver Arthritis Clinic /ID# 135901

Denver, Colorado, United States

New England Research Associates, LLC /ID# 124085

Bridgeport, Connecticut, United States

Arthritis & Rheumatic Disease Specialties /ID# 135910

Aventura, Florida, United States

Rheumatology Associates of South Florida (RASF) - Clinical Research /ID# 124082

Boca Raton, Florida, United States

Omega Research Maitland, LLC /ID# 124094

DeBary, Florida, United States

University of Florida /ID# 124087

Jacksonville, Florida, United States

Suncoast Research Group /ID# 137774

Miami, Florida, United States

Omega Research Maitland, LLC /ID# 137398

Orlando, Florida, United States

Millennium Research /ID# 135917

Ormond Beach, Florida, United States

Arthritis Center, Inc. /ID# 124090

Palm Harbor, Florida, United States

IRIS Research and Development, LLC /ID# 140362

Plantation, Florida, United States

Lovelace Scientific Resources /ID# 128745

Venice, Florida, United States

North Georgia Rheumatology Group /ID# 128746

Lawrenceville, Georgia, United States

Kansas City Internal Medicine /ID# 135916

Overland Park, Kansas, United States

PRN Professional Research Network of Kansas, LLC /ID# 124091

Wichita, Kansas, United States

Klein and Associates MD - Hagerstown /ID# 124086

Hagerstown, Maryland, United States

The Center for Rheumatology and Bone Research /ID# 124077

Wheaton, Maryland, United States

Clinical Pharmacology Study Group /ID# 124079

Worcester, Massachusetts, United States

June DO, PC /ID# 124081

Lansing, Michigan, United States

Summit Medical Group /ID# 124076

Clifton, New Jersey, United States

Arthritis and Osteoporosis Associates /ID# 135907

Freehold, New Jersey, United States

Arthritis Rheumatic and Back Disease Associates. P.A. /ID# 135913

Voorhees Township, New Jersey, United States

Arthritis and Osteo Assoc /ID# 132280

Las Cruces, New Mexico, United States

DJL Clinical Research, PLLC /ID# 131936

Charlotte, North Carolina, United States

Cincinnati Rheumatic Disease Study Group, Inc. /ID# 135921

Cincinnati, Ohio, United States

STAT Research, Inc. /ID# 134906

Vandalia, Ohio, United States

Health Research of Oklahoma /ID# 135904

Oklahoma City, Oklahoma, United States

Duplicate_East Penn Rheumatology Assoc /ID# 135920

Bethlehem, Pennsylvania, United States

Altoona Ctr Clinical Res /ID# 124089

Duncansville, Pennsylvania, United States

Emkey Arthritis and Osteoporosis Clinic /ID# 135908

Wyomissing, Pennsylvania, United States

Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 124080

Summerville, South Carolina, United States

Dr. Ramesh Gupta /ID# 128744

Memphis, Tennessee, United States

Austin Rheumatology Research /ID# 124083

Austin, Texas, United States

Accurate Clinical Management /ID# 128751

Baytown, Texas, United States

Accurate Clinical Management /ID# 128752

Houston, Texas, United States

Baylor College of Medicine - Baylor Medical Center /ID# 135905

Houston, Texas, United States

Houston Institute for Clin Res /ID# 135912

Houston, Texas, United States

Accurate Clinical Research /ID# 128753

Houston, Texas, United States

Accurate Clinical Research /ID# 128754

Houston, Texas, United States

SW Rheumatology Res. LLC /ID# 135927

Mesquite, Texas, United States

Mountain State Clinical Research /ID# 124088

Clarksburg, West Virginia, United States

Aurora Rheumatology and Immunotherapy Center /ID# 135922

Franklin, Wisconsin, United States

UCL Saint-Luc /ID# 139348

Woluwe-Saint-Lambert, Brussels Capital, Belgium

ReumaClinic Genk-Hasselt /ID# 137775

Genk, , Belgium

MHAT Trimontsium /ID# 135328

Plovdiv, , Bulgaria

Duplicate_MHAT Kaspela /ID# 136212

Plovdiv, , Bulgaria

UHMAT Palmed Plovdiv /ID# 135355

Plovdiv, , Bulgaria

UMHAT Sveti Ivan Rilski /ID# 135678

Sofia, , Bulgaria

UMHAT Sveti Ivan Rilski /ID# 136210

Sofia, , Bulgaria

Diagnostic Consultative Center /ID# 136736

Sofia, , Bulgaria

Diagnostic consultative center Equita /ID# 136209

Varna, , Bulgaria

Corporacion de Beneficiencia Osorno /ID# 136189

Osorno, Los Lagos Region, Chile

Quantum Research /ID# 136188

Puerto Varas, Los Lagos Region, Chile

Duplicate_Artroscan s.r.o. /ID# 139347

Ostrava, , Czechia

L.K.N. Arthrocentrum, s.r.o /ID# 128782

Petřkovice, , Czechia

Revmatologicky ustav v Praze /ID# 137937

Prague, , Czechia

Revmatologicka ambulance - MUDr. Zuzana Urbanova /ID# 137776

Prague, , Czechia

Revmatologie Bruntal, s.r.o /ID# 137782

Prostějov, , Czechia

Qualiclinic Kft. /ID# 134170

Budapest, Pest County, Hungary

Orszagos Reumatologiai es Fizioterapias Intezet /ID# 128785

Budapest, , Hungary

Szent Margit Szakrendelo /ID# 136676

Budapest, , Hungary

MAV Korhaz ess Rendelointezet /ID# 139971

Szolnok, , Hungary

Veszprem Megyei Csolnoky Ferenc Korhaz /ID# 128784

Veszprém, , Hungary

The Chaim Sheba Medical Center /ID# 139295

Ramat Gan, Tel Aviv, Israel

Barzilai Medical Center /ID# 140199

Ashkelon, , Israel

M & M Centrs LTD /ID# 132439

Ādaži, , Latvia

Arija's Ancane's Family Doctor Practice /ID# 132437

Baldone, , Latvia

Clinic ORTO /ID# 132438

Riga, , Latvia

Clinstile, S.A. de C.V. /ID# 137075

Cuauhtémoc, Mexico City, Mexico

Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 137307

Mexico City, , Mexico

Cliditer SA de CV /ID# 136876

Mexico City, , Mexico

Timaru Medical Specialists Ltd /ID# 131909

Timaru, Canterbury, New Zealand

Waikato Hospital /ID# 131908

Hamilton, Waikato Region, New Zealand

Porter Rheumatology Ltd /ID# 133983

Nelson, , New Zealand

Prywatna Praktyka Lekarska /ID# 128837

Poznan, Greater Poland Voivodeship, Poland

Pratia MCM Krakow /ID# 134749

Krakow, Lesser Poland Voivodeship, Poland

Reum-Medica S.C. /ID# 128841

Wroclaw, Lower Silesian Voivodeship, Poland

Twoja Przychodnia Centrum Medyczne /ID# 128840

Nowa Sól, Lubusz Voivodeship, Poland

NZOZ Lecznica MAK-MED s.c. /ID# 128838

Nadarzyn, Masovian Voivodeship, Poland

Medicome sp. z o.o. /ID# 137397

Oswiecim, Masovian Voivodeship, Poland

NBR Polska /ID# 136208

Warsaw, Masovian Voivodeship, Poland

Centrum Medyczne Amed Warszawa Zoliborz /ID# 128835

Warsaw, Masovian Voivodeship, Poland

Centrum Medyczne Pratia Warszawa /ID# 136650

Warsaw, Masovian Voivodeship, Poland

Centrum Medyczne Reuma Park w Warszawie /ID# 140198

Warsaw, Masovian Voivodeship, Poland

Gabinet Internistyczno-Reumatologiczny /ID# 135876

Bialystok, Podlaskie Voivodeship, Poland

Centrum Medyczne Pratia Gdynia /ID# 137362

Gdynia, Pomeranian Voivodeship, Poland

Ambulatorium Sp. z o.o /ID# 138074

Elblag, Warmian-Masurian Voivodeship, Poland

Duplicate_REUMED Filia nr 2 /ID# 128839

Lublin, , Poland

Dr. Ramon L. Ortega-Colon, MD /ID# 128760

Carolina, , Puerto Rico

GCM Medical Group PSC - Hato Rey /ID# 128759

San Juan, , Puerto Rico

Mindful Medical Research /ID# 136211

San Juan, , Puerto Rico

Kazan State Medical University /ID# 136734

Kazan', Tatarstan, Respublika, Russia

Tver Regional Clinical Hospital /ID# 137576

Tver', Tver Oblast, Russia

St. Petersburg Research Institute of Emergency Medicine n.а. I. I. Dzhanelidze /ID# 136652

Saint Petersburg, , Russia

MEDMAN s.r.o. /ID# 136649

Martin, , Slovakia

Poliklinika Senica n.o. /ID# 134728

Senica, , Slovakia

Dr MJ Prins /ID# 138540

Cape Town, Western Cape, South Africa

Winelands Medical Research Centre /ID# 134669

Stellenbosch, Western Cape, South Africa

Clinica Gaias /ID# 133868

Santiago de Compostela, A Coruna, Spain

Hospital General Universitario de Elche /ID# 128851

Elche, Alicante, Spain

Hospital Infanta Sofia /ID# 136653

San Sebastián de los Reyes, Madrid, Spain

Hospital Regional de Malaga /ID# 128847

Málaga, Malaga, Spain

Hospital Universitario A Coruna - CHUAC /ID# 128846

A Coruña, , Spain

Hospital CIMA Sanitas /ID# 128849

Barcelona, , Spain

Hospital Clinico Universitario San Carlos /ID# 128852

Madrid, , Spain

Hospital Universitario Virgen Macarena /ID# 128853

Seville, , Spain

Hospital QuironSalud Infanta Luisa /ID# 135689

Seville, , Spain

Hospital Universitario Virgen de Valme /ID# 134668

Seville, , Spain

NSC Strazhesko Ist Cardiology /ID# 137330

Kiev, , Ukraine

Municipal Non-profit Institution Kyiv City Clinical Hospital No. 3 of the Exec /ID# 137334

Kyiv, , Ukraine

Warrington and Halton Hospitals NHS Foundation Trust /ID# 137514

Warrington, Cheshire West And Chester, United Kingdom

Barts Health NHS Trust /ID# 135683

London, London, City of, United Kingdom

West Suffolk Hospital /ID# 128858

Bury St Edmunds, Suffolk, United Kingdom

Duplicate_Leeds Teaching Hospitals NHS Trust /ID# 141308

Leeds, , United Kingdom

Countries

United States; Belgium; Bulgaria; Chile; Czechia; Hungary; Israel; Latvia; Mexico; New Zealand; Poland; Puerto Rico; Russia; Slovakia; South Africa; Spain; Ukraine; United Kingdom

References

Baraliakos X, van der Heijde D, Sieper J, Inman RD, Kameda H, Li Y, Bu X, Shmagel A, Wung P, Song IH, Deodhar A. Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study. Arthritis Res Ther. 2023 Sep 18;25(1):172. doi: 10.1186/s13075-023-03128-1.

Reference Type: DERIVED

PMID: 37723577 (View on PubMed)

Kivitz A, Wells AF, Vargas JI, Baraf HSB, Rischmueller M, Klaff J, Khan N, Li Y, Carter K, Friedman A, Durez P. Long-Term Efficacy and Safety of Upadacitinib in Patients with Rheumatoid Arthritis: Final Results from the BALANCE-EXTEND Open-Label Extension Study. Rheumatol Ther. 2023 Aug;10(4):901-915. doi: 10.1007/s40744-023-00557-x. Epub 2023 May 18.

Reference Type: DERIVED

PMID: 37199884 (View on PubMed)

Winthrop K, Vargas JI, Drescher E, Garcia C, Friedman A, Hendrickson B, Li Y, Klaff J, Kivitz A. Evaluation of response to 13-valent conjugated pneumococcal vaccination in patients with rheumatoid arthritis receiving upadacitinib: results from a phase 2 open-label extension study. RMD Open. 2022 Mar;8(1):e002110. doi: 10.1136/rmdopen-2021-002110.

Reference Type: DERIVED

PMID: 35246470 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.rxabbvie.com/

Related Info.

Other Identifiers

2013-003530-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M13-538

Identifier Type: -

Identifier Source: org_study_id