An Open-label Extension Study Evaluating the Safety and Efficacy of Upadacitinib (ABT-494) in Adults With Rheumatoid Arthritis (BALANCE-EXTEND)
Rheumatoid Arthritis
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Musculoskeletal Disease, Arthritis, Joint Diseases, Anti-inflammatory Agents, Antirheumatic agents
Eligibility Criteria
Inclusion Criteria:
- Subjects who have completed Study M13-550 (NCT01960855) or Study M13-537 (NCT02066389) with upadacitinib (ABT-494) and did not develop any discontinuation criteria.
- 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.
- 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.
- 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:
- Must currently be enrolled in the main study.
- 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.
- 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.
- 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.
- Must meet the prescribing specifications as per local label requirements to receive Prevnar 13® vaccine.
- Willing to receive Prevnar13® vaccine.
Exclusion Criteria:
- Pregnant or breastfeeding female.
- 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.
- Anticipated requirement or receipt of any live vaccine during study participation including up to 30 days after the last dose of study drug.
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
- Enrollment in another interventional clinical study while participating in this study.
- Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive study drug.
Substudy:
- Receiving any conventional synthetic disease modifying antirheumatic drugs (csDMARDs) other than methotrexate
- Receiving > 10 mg/day of prednisone or equivalent corticosteroid therapy.
- Receipt of any steroid injection within 4 weeks prior to Vaccination visit.
- History of severe allergic reaction (e.g., anaphylaxis) to any component of Prevnar 13®.
- History of any documented pneumococcal infection within the last 6 months prior to the vaccination visit.
- Receipt of any vaccine 4 weeks prior to the vaccination visit and/or anticipation of any vaccination for 4 weeks after the vaccination visit.
- Receipt of any pneumococcal vaccine.
- Subject is not suitable for the sub-study as per the Investigator's judgment.
Sites / Locations
- Rheum Assoc of North Alabama /ID# 135926
- AZ Arthritis and Rheumotology Research, PLLC /ID# 135902
- AZ Arthritis and Rheumotology Research, PLLC /ID# 135931
- C.V. Mehta MD, Med Corporation /ID# 124092
- Moores Cancer Center at UC San Diego /ID# 128747
- Desert Medical Advances - Palm Desert /ID# 135911
- Orrin Troum, M.D. and Medical /ID# 135933
- Duplicate_Robin K. Dore MD, Inc /ID# 135906
- Inland Rheum Clin Trials Inc. /ID# 136716
- Duplicate_Desert Valley Medical Group /ID# 135932
- Denver Arthritis Clinic /ID# 135901
- New England Research Associates, LLC /ID# 124085
- Arthritis & Rheumatic Disease Specialties /ID# 135910
- Rheumatology Associates of South Florida (RASF) - Clinical Research /ID# 124082
- Omega Research Maitland, LLC /ID# 124094
- University of Florida /ID# 124087
- Suncoast Research Group /ID# 137774
- Omega Research Maitland, LLC /ID# 137398
- Millennium Research /ID# 135917
- Arthritis Center, Inc. /ID# 124090
- IRIS Research and Development, LLC /ID# 140362
- Lovelace Scientific Resources /ID# 128745
- North Georgia Rheumatology Group /ID# 128746
- Kansas City Internal Medicine /ID# 135916
- PRN Professional Research Network of Kansas, LLC /ID# 124091
- Klein and Associates MD - Hagerstown /ID# 124086
- The Center for Rheumatology and Bone Research /ID# 124077
- Clinical Pharmacology Study Group /ID# 124079
- June DO, PC /ID# 124081
- Summit Medical Group /ID# 124076
- Arthritis and Osteoporosis Associates /ID# 135907
- Arthritis Rheumatic and Back Disease Associates. P.A. /ID# 135913
- Arthritis and Osteo Assoc /ID# 132280
- DJL Clinical Research, PLLC /ID# 131936
- Cincinnati Rheumatic Disease Study Group, Inc. /ID# 135921
- STAT Research, Inc. /ID# 134906
- Health Research of Oklahoma /ID# 135904
- Duplicate_East Penn Rheumatology Assoc /ID# 135920
- Altoona Ctr Clinical Res /ID# 124089
- Emkey Arthritis and Osteoporosis Clinic /ID# 135908
- Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 124080
- Dr. Ramesh Gupta /ID# 128744
- Austin Rheumatology Research /ID# 124083
- Accurate Clinical Management /ID# 128751
- Accurate Clinical Management /ID# 128752
- Baylor College of Medicine - Baylor Medical Center /ID# 135905
- Houston Institute for Clin Res /ID# 135912
- Accurate Clinical Research /ID# 128753
- Accurate Clinical Research /ID# 128754
- SW Rheumatology Res. LLC /ID# 135927
- Mountain State Clinical Research /ID# 124088
- Aurora Rheumatology and Immunotherapy Center /ID# 135922
- UCL Saint-Luc /ID# 139348
- ReumaClinic Genk-Hasselt /ID# 137775
- MHAT Trimontsium /ID# 135328
- Duplicate_MHAT Kaspela /ID# 136212
- UHMAT Palmed Plovdiv /ID# 135355
- UMHAT Sveti Ivan Rilski /ID# 135678
- UMHAT Sveti Ivan Rilski /ID# 136210
- Diagnostic Consultative Center /ID# 136736
- Diagnostic consultative center Equita /ID# 136209
- Corporacion de Beneficiencia Osorno /ID# 136189
- Quantum Research /ID# 136188
- Duplicate_Artroscan s.r.o. /ID# 139347
- L.K.N. Arthrocentrum, s.r.o /ID# 128782
- Revmatologicky ustav v Praze /ID# 137937
- Revmatologicka ambulance - MUDr. Zuzana Urbanova /ID# 137776
- Revmatologie Bruntal, s.r.o /ID# 137782
- Qualiclinic Kft. /ID# 134170
- Orszagos Reumatologiai es Fizioterapias Intezet /ID# 128785
- Szent Margit Szakrendelo /ID# 136676
- MAV Korhaz ess Rendelointezet /ID# 139971
- Veszprem Megyei Csolnoky Ferenc Korhaz /ID# 128784
- The Chaim Sheba Medical Center /ID# 139295
- Barzilai Medical Center /ID# 140199
- M & M Centrs LTD /ID# 132439
- Arija's Ancane's Family Doctor Practice /ID# 132437
- Clinic ORTO /ID# 132438
- Clinstile, S.A. de C.V. /ID# 137075
- Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 137307
- Cliditer SA de CV /ID# 136876
- Timaru Medical Specialists Ltd /ID# 131909
- Waikato Hospital /ID# 131908
- Porter Rheumatology Ltd /ID# 133983
- Reum-Medica S.C. /ID# 128841
- Twoja Przychodnia Centrum Medyczne /ID# 128840
- Pratia MCM Krakow /ID# 134749
- NZOZ Lecznica MAK-MED s.c. /ID# 128838
- Medicome sp. z o.o. /ID# 137397
- Centrum Medyczne Amed Warszawa Zoliborz /ID# 128835
- Centrum Medyczne Pratia Warszawa /ID# 136650
- Centrum Medyczne Reuma Park w Warszawie /ID# 140198
- NBR Polska /ID# 136208
- Gabinet Internistyczno-Reumatologiczny /ID# 135876
- Centrum Medyczne Pratia Gdynia /ID# 137362
- Ambulatorium Sp. z o.o /ID# 138074
- Prywatna Praktyka Lekarska /ID# 128837
- Duplicate_REUMED Filia nr 2 /ID# 128839
- Dr. Ramon L. Ortega-Colon, MD /ID# 128760
- GCM Medical Group PSC - Hato Rey /ID# 128759
- Mindful Medical Research /ID# 136211
- Kazan State Medical University /ID# 136734
- Tver Regional Clinical Hospital /ID# 137576
- St. Petersburg Research Institute of Emergency Medicine n.а. I. I. Dzhanelidze /ID# 136652
- MEDMAN s.r.o. /ID# 136649
- Poliklinika Senica n.o. /ID# 134728
- Dr MJ Prins /ID# 138540
- Winelands Medical Research Centre /ID# 134669
- Clinica Gaias /ID# 133868
- Hospital General Universitario de Elche /ID# 128851
- Hospital Infanta Sofia /ID# 136653
- Hospital Regional de Malaga /ID# 128847
- Hospital Universitario A Coruna - CHUAC /ID# 128846
- Hospital CIMA Sanitas /ID# 128849
- Hospital Clinico Universitario San Carlos /ID# 128852
- Hospital Universitario Virgen Macarena /ID# 128853
- Hospital QuironSalud Infanta Luisa /ID# 135689
- Hospital Universitario Virgen de Valme /ID# 134668
- NSC Strazhesko Ist Cardiology /ID# 137330
- Municipal Non-profit Institution Kyiv City Clinical Hospital No. 3 of the Exec /ID# 137334
- Warrington and Halton Hospitals NHS Foundation Trust /ID# 137514
- Barts Health NHS Trust /ID# 135683
- West Suffolk Hospital /ID# 128858
- Duplicate_Leeds Teaching Hospitals NHS Trust /ID# 141308
Arms of the Study
Arm 1
Experimental
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).