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

Phase 2 Study, Multicenter, Open-Label Extension (OLE) Study in Rheumatoid Arthritis Subjects Who Have Completed a Preceding Phase 2 Randomized Controlled Trial (RCT) With Upadacitinib (ABT-494)

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Upadacitinib; Biological: Pneumococcal 13-valent conjugate vaccine (PCV-13)

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.

• Study Type: Interventional
• Enrollment (Actual): 493
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Genk, Belgium, 3600
    • ReumaClinic Genk-Hasselt /ID# 137775
  • Bruxelles-Capitale
    • Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium, 1200
      • UCL Saint-Luc /ID# 139348
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • MHAT Trimontsium /ID# 135328
  • Plovdiv, Bulgaria, 4001
    • Duplicate_MHAT Kaspela /ID# 136212
  • Plovdiv, Bulgaria, 4002
    • UHMAT Palmed Plovdiv /ID# 135355
  • Sofia, Bulgaria, 1431
    • UMHAT Sveti Ivan Rilski /ID# 135678
  • Sofia, Bulgaria, 1431
    • UMHAT Sveti Ivan Rilski /ID# 136210
  • Sofia, Bulgaria, 1612
    • Diagnostic Consultative Center /ID# 136736
  • Varna, Bulgaria, 9000
    • Diagnostic consultative center Equita /ID# 136209
• Chile
  • Los Lagos
    • Osorno, Los Lagos, Chile, 1710216
      • Corporacion de Beneficiencia Osorno /ID# 136189
    • Puerto Varas, Los Lagos, Chile, 5550170
      • Quantum Research /ID# 136188
• Czechia
  • Ostrava, Czechia, 722 00
    • Duplicate_Artroscan s.r.o. /ID# 139347
  • Petrkovice, Czechia, 725 29
    • L.K.N. Arthrocentrum, s.r.o /ID# 128782
  • Praha, Czechia, 128 00
    • Revmatologicky ustav v Praze /ID# 137937
  • Praha, Czechia, 140 00
    • Revmatologicka ambulance - MUDr. Zuzana Urbanova /ID# 137776
  • Prostejov, Czechia, 796 01
    • Revmatologie Bruntal, s.r.o /ID# 137782
• Hungary
  • Budapest, Hungary, 1023
    • Orszagos Reumatologiai es Fizioterapias Intezet /ID# 128785
  • Budapest, Hungary, 1032
    • Szent Margit Szakrendelo /ID# 136676
  • Szolnok, Hungary, 5000
    • MAV Korhaz ess Rendelointezet /ID# 139971
  • Veszprem, Hungary, 8200
    • Veszprem Megyei Csolnoky Ferenc Korhaz /ID# 128784
  • Pest
    • Budapest, Pest, Hungary, 1036
      • Qualiclinic Kft. /ID# 134170
• Israel
  • Ashkelon, Israel, 7830604
    • Barzilai Medical Center /ID# 140199
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 139295
• Latvia
  • Adazi, Latvia, LV-2164
    • M & M Centrs LTD /ID# 132439
  • Baldone, Latvia, LV-2125
    • Arija's Ancane's Family Doctor Practice /ID# 132437
  • Riga, Latvia, LV-1005
    • Clinic ORTO /ID# 132438
• Mexico
  • Mexico City, Mexico, 06090
    • Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 137307
  • Mexico City, Mexico, 06700
    • Cliditer SA de CV /ID# 136876
  • Ciudad De Mexico
    • Cuauhtemoc, Ciudad De Mexico, Mexico, 20313
      • Clinstile, S.A. de C.V. /ID# 137075
• New Zealand
  • Nelson, New Zealand, 7010
    • Porter Rheumatology Ltd /ID# 133983
  • Canterbury
    • Timaru, Canterbury, New Zealand, 7910
      • Timaru Medical Specialists Ltd /ID# 131909
  • Waikato
    • Hamilton, Waikato, New Zealand, 3240
      • Waikato Hospital /ID# 131908
• Poland
  • Lublin, Poland, 20-582
    • Duplicate_REUMED Filia nr 2 /ID# 128839
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-244
      • Reum-Medica S.C. /ID# 128841
  • Lubuskie
    • Nowa Sol, Lubuskie, Poland, 67-100
      • Twoja Przychodnia Centrum Medyczne /ID# 128840
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-510
      • Pratia MCM Krakow /ID# 134749
  • Mazowieckie
    • Nadarzyn, Mazowieckie, Poland, 05-830
      • NZOZ Lecznica MAK-MED s.c. /ID# 128838
    • Oswiecim, Mazowieckie, Poland, 32-600
      • Medicome sp. z o.o. /ID# 137397
    • Warsaw, Mazowieckie, Poland, 01-518
      • Centrum Medyczne Amed Warszawa Zoliborz /ID# 128835
    • Warsaw, Mazowieckie, Poland, 01-868
      • Centrum Medyczne Pratia Warszawa /ID# 136650
    • Warsaw, Mazowieckie, Poland, 02-691
      • Centrum Medyczne Reuma Park w Warszawie /ID# 140198
    • Warszawa, Mazowieckie, Poland, 00-465
      • NBR Polska /ID# 136208
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-077
      • Gabinet Internistyczno-Reumatologiczny /ID# 135876
  • Pomorskie
    • Gdynia, Pomorskie, Poland, 81-338
      • Centrum Medyczne Pratia Gdynia /ID# 137362
  • Warminsko-mazurskie
    • Elblag, Warminsko-mazurskie, Poland, 82-300
      • Ambulatorium Sp. z o.o /ID# 138074
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 61-397
      • Prywatna Praktyka Lekarska /ID# 128837
• Puerto Rico
  • Carolina, Puerto Rico, 00983
    • Dr. Ramon L. Ortega-Colon, MD /ID# 128760
  • San Juan, Puerto Rico, 00917-3104
    • GCM Medical Group PSC - Hato Rey /ID# 128759
  • San Juan, Puerto Rico, 00918-3756
    • Mindful Medical Research /ID# 136211
• Russian Federation
  • Sankt-Peterburg, Russian Federation, 192242
    • St. Petersburg Research Institute of Emergency Medicine n.а. I. I. Dzhanelidze /ID# 136652
  • Tatarstan, Respublika
    • Kazan, Tatarstan, Respublika, Russian Federation, 420012
      • Kazan State Medical University /ID# 136734
  • Tverskaya Oblast
    • Tver, Tverskaya Oblast, Russian Federation, 170036
      • Tver Regional Clinical Hospital /ID# 137576
• Slovakia
  • Martin, Slovakia, 036 01
    • MEDMAN s.r.o. /ID# 136649
  • Senica, Slovakia, 905 01
    • Poliklinika Senica n.o. /ID# 134728
• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7500
      • Dr MJ Prins /ID# 138540
    • Stellenbosch, Western Cape, South Africa, 7600
      • Winelands Medical Research Centre /ID# 134669
• Spain
  • A Coruna, Spain, 15006
    • Hospital Universitario A Coruna - CHUAC /ID# 128846
  • Barcelona, Spain, 08034
    • Hospital CIMA Sanitas /ID# 128849
  • Madrid, Spain, 28040
    • Hospital Clinico Universitario San Carlos /ID# 128852
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena /ID# 128853
  • Sevilla, Spain, 41010
    • Hospital QuironSalud Infanta Luisa /ID# 135689
  • Sevilla, Spain, 41014
    • Hospital Universitario Virgen de Valme /ID# 134668
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15702
      • Clinica Gaias /ID# 133868
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche /ID# 128851
  • Madrid
    • San Sebastián de Los Reyes, Madrid, Spain, 28702
      • Hospital Infanta Sofia /ID# 136653
  • Malaga
    • Málaga, Malaga, Spain, 29010
      • Hospital Regional de Malaga /ID# 128847
• Ukraine
  • Kiev, Ukraine, 03680
    • NSC Strazhesko Ist Cardiology /ID# 137330
  • Kyiv, Ukraine, 02125
    • Municipal Non-profit Institution Kyiv City Clinical Hospital No. 3 of the Exec /ID# 137334
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Duplicate_Leeds Teaching Hospitals NHS Trust /ID# 141308
  • Cheshire West And Chester
    • Warrington, Cheshire West And Chester, United Kingdom, WA5 1QG
      • Warrington and Halton Hospitals NHS Foundation Trust /ID# 137514
  • London, City Of
    • London, London, City Of, United Kingdom, E1 2ES
      • Barts Health NHS Trust /ID# 135683
  • Suffolk
    • Bury St Edmunds, Suffolk, United Kingdom, IP33 2QZ
      • West Suffolk Hospital /ID# 128858
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Rheum Assoc of North Alabama /ID# 135926
  • Arizona
    • Phoenix, Arizona, United States, 85032-9306
      • AZ Arthritis and Rheumotology Research, PLLC /ID# 135902
    • Phoenix, Arizona, United States, 85032-9306
      • AZ Arthritis and Rheumotology Research, PLLC /ID# 135931
  • California
    • Hemet, California, United States, 92543
      • C.V. Mehta MD, Med Corporation /ID# 124092
    • La Jolla, California, United States, 92093
      • Moores Cancer Center at UC San Diego /ID# 128747
    • Palm Desert, California, United States, 92260
      • Desert Medical Advances - Palm Desert /ID# 135911
    • Santa Monica, California, United States, 90404
      • Orrin Troum, M.D. and Medical /ID# 135933
    • Tustin, California, United States, 92780
      • Duplicate_Robin K. Dore MD, Inc /ID# 135906
    • Upland, California, United States, 91786
      • Inland Rheum Clin Trials Inc. /ID# 136716
    • Victorville, California, United States, 92395
      • Duplicate_Desert Valley Medical Group /ID# 135932
  • Colorado
    • Denver, Colorado, United States, 80230
      • Denver Arthritis Clinic /ID# 135901
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606-1827
      • New England Research Associates, LLC /ID# 124085
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis & Rheumatic Disease Specialties /ID# 135910
    • Boca Raton, Florida, United States, 33486
      • Rheumatology Associates of South Florida (RASF) - Clinical Research /ID# 124082
    • DeBary, Florida, United States, 32713-2260
      • Omega Research Maitland, LLC /ID# 124094
    • Jacksonville, Florida, United States, 32209
      • University of Florida /ID# 124087
    • Miami, Florida, United States, 33135
      • Suncoast Research Group /ID# 137774
    • Orlando, Florida, United States, 32808
      • Omega Research Maitland, LLC /ID# 137398
    • Ormond Beach, Florida, United States, 32174
      • Millennium Research /ID# 135917
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Center, Inc. /ID# 124090
    • Plantation, Florida, United States, 33324
      • IRIS Research and Development, LLC /ID# 140362
    • Venice, Florida, United States, 34292
      • Lovelace Scientific Resources /ID# 128745
  • Georgia
    • Lawrenceville, Georgia, United States, 30045
      • North Georgia Rheumatology Group /ID# 128746
  • Kansas
    • Overland Park, Kansas, United States, 66209
      • Kansas City Internal Medicine /ID# 135916
    • Wichita, Kansas, United States, 67205
      • PRN Professional Research Network of Kansas, LLC /ID# 124091
  • Maryland
    • Hagerstown, Maryland, United States, 21742
      • Klein and Associates MD - Hagerstown /ID# 124086
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research /ID# 124077
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Group /ID# 124079
  • Michigan
    • Lansing, Michigan, United States, 48910
      • June DO, PC /ID# 124081
  • New Jersey
    • Clifton, New Jersey, United States, 07012-1647
      • Summit Medical Group /ID# 124076
    • Freehold, New Jersey, United States, 07728-8307
      • Arthritis and Osteoporosis Associates /ID# 135907
    • Voorhees, New Jersey, United States, 08043
      • Arthritis Rheumatic and Back Disease Associates. P.A. /ID# 135913
  • New Mexico
    • Las Cruces, New Mexico, United States, 88011
      • Arthritis and Osteo Assoc /ID# 132280
  • North Carolina
    • Charlotte, North Carolina, United States, 28210-8508
      • DJL Clinical Research, PLLC /ID# 131936
  • Ohio
    • Cincinnati, Ohio, United States, 45242-4468
      • Cincinnati Rheumatic Disease Study Group, Inc. /ID# 135921
    • Vandalia, Ohio, United States, 45377-9464
      • STAT Research, Inc. /ID# 134906
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103-2400
      • Health Research of Oklahoma /ID# 135904
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Duplicate_East Penn Rheumatology Assoc /ID# 135920
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Ctr Clinical Res /ID# 124089
    • Wyomissing, Pennsylvania, United States, 19610
      • Emkey Arthritis and Osteoporosis Clinic /ID# 135908
  • South Carolina
    • Summerville, South Carolina, United States, 29486-7887
      • Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 124080
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Dr. Ramesh Gupta /ID# 128744
  • Texas
    • Austin, Texas, United States, 78705
      • Austin Rheumatology Research /ID# 124083
    • Baytown, Texas, United States, 77521
      • Accurate Clinical Management /ID# 128751
    • Houston, Texas, United States, 77004
      • Accurate Clinical Management /ID# 128752
    • Houston, Texas, United States, 77030-3411
      • Baylor College of Medicine - Baylor Medical Center /ID# 135905
    • Houston, Texas, United States, 77074
      • Houston Institute for Clin Res /ID# 135912
    • Houston, Texas, United States, 77089
      • Accurate Clinical Research /ID# 128753
    • Houston, Texas, United States, 77089
      • Accurate Clinical Research /ID# 128754
    • Mesquite, Texas, United States, 75150
      • SW Rheumatology Res. LLC /ID# 135927
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Mountain State Clinical Research /ID# 124088
  • Wisconsin
    • Franklin, Wisconsin, United States, 53132
      • Aurora Rheumatology and Immunotherapy Center /ID# 135922

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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).

Drug: Upadacitinib; Tablet taken orally; Other Names: ABT-494; RINVOQ®; Biological: Pneumococcal 13-valent conjugate vaccine (PCV-13); Administered by intramuscular injection; Other Names: Prevnar 13®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Over Time	Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count;; ≥ 20% improvement in 66-swollen joint count; and; ≥ 20% improvement in at least 3 of the 5 following parameters:Physician global assessment of disease activityPatient global assessment of disease activityPatient assessment of painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP).	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response Over Time	Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria: ≥ 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 global assessment of disease activityPatient global assessment of disease activityPatient assessment of painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP).	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response Over Time	Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria: ≥ 70% improvement in 68-tender joint count;; ≥ 70% improvement in 66-swollen joint count; and; ≥ 70% improvement in at least 3 of the 5 following parameters:Physician global assessment of disease activityPatient global assessment of disease activityPatient assessment of painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP).	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Percentage of Participants With Satisfactory Humoral Response to PCV-13 Four Weeks After Vaccination	Satisfactory humoral response is defined as greater than or equal to 2-fold increase in antibody concentration from the vaccination Baseline in at least 6 out of the 12 pneumococcal antigens 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F).	Vaccination Baseline (defined as the last non-missing observation on or before the date of receiving PCV-13 vaccination) and 4 weeks after vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time	The DAS28(CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. LDA is defined as a DAS28(CRP) score ≤ 3.2.	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time	The DAS28 (CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical remission is defined as a DAS28(CRP) score < 2.6.	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Over Time	The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's 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.	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Over Time	The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's 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. Clinical remission is defined as a CDAI score ≤ 2.8.	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Simplified Disease Activity Index (SDAI) Over Time	The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity. LDA is defined as a SDAI score ≤ 11.0.	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Percentage of Participants Achieving Clinical Remission (CR) Based on Simplified Disease Activity Index (SDAI) Over Time	The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity. Clinical remission is defined as a SDAI score ≤ 3.3.	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) Over Time	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 approximately 10 where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in Clinical Disease Activity Index (CDAI) Over Time	The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's 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. A negative change from Baseline indicates improvement in disease activity.	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in SimplifiedDisease Activity Index (SDAI) Over Time	The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in Tender Joint Count (TJC68) Over Time	Sixty-eight joints were assessed by an evaluator for tenderness or pain. The presence of tenderness was scored as a "1" and absence of tenderness as a "0". The total tender joint count is the sum of the scores, and ranges from 0 to 68 (worst).	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in Swollen Joint Count (SJC66) Over Time	Sixty-six joints were assessed by an evaluator for swelling. The presence of swelling was scored as a "1" and absence of swelling as a "0". The total swollen joint count is the sum of the scores, and ranges from 0 to 66 (worst).	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in Physician's Global Assessment of Disease Activity Over Time	The physician rated the participant's current global RA disease activity (independently from the participant's assessment) on a visual analog scale (VAS) from 0 to 100 mm, where 0 mm indicates no disease activity and 100 mm indicates severe disease activity	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in Patient's Global Assessment of Disease Activity Over Time	The participant was asked to rate their current RA disease activity over the past 24 hours on a 100 mm VAS, where 0 mm indicates very low disease activity and 100 mm indicates very high disease activity.	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in Patient's Assessment of Pain Over Time	Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale from 0 to 100 mm. A score of 0 mm indicates "no pain" and a score of 100 mm indicates "worst possible pain."	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Over Time	The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) Over Time		Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Over Time	The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better quality of life. A positive change from Baseline indicates improvement.	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in Work Instability Scale for RA (RA-WIS) Over Time	RA-WIS is a tool to evaluate work instability (the consequence of a mismatch between an individual's functional ability and their work tasks). RA-WIS consists of 23 questions relating to the participant's functioning in their work environment, each answered as Yes or No. The total score is the number of questions answered Yes, and ranges from 0 to 23. A score < 10 means low risk, scores between 10 and 17 indicate medium risk, and scores > 17 indicate high risk of work instability. A negative change from Baseline indicates improvement in work instability.	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in EuroQoL-5D (EQ-5D) Index Over Time	The EQ-5D-5L is a generic measure of health status consisting of two parts. The first part (the descriptive system) assesses health in five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which is rated on 5 levels of severity (1: no problem, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems). A health state index score was calculated from individual health profiles using a UK scoring algorithm. Health state index scores generally range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility. The higher the score the better the health status. A positive change from baseline indicates improvement in health status.	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Change From Baseline in EuroQoL-5D VAS Score Over Time	The EQ-5D-5L is a generic measure of health status consisting of two parts. The second part of the questionnaire consists of a visual analog scale (VAS) on which the participant rates his/her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health). A positive change from baseline indicates improvement.	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312
Percentage of Participants With Satisfactory Humoral Response to PCV-13 12 Weeks After Vaccination	Satisfactory humoral response is defined as greater than or equal to 2-fold increase in antibody concentration from the vaccination Baseline in at least 6 out of the 12 pneumococcal antigens 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F).	Vaccination Baseline and 12 weeks after vaccination
Geometric Mean Fold Rise (GMFR) of Anti-pneumococcal Antibody Levels to Each of the 12 Pneumococcal Antigens 4 and 12 Weeks After Vaccination		Vaccination Baseline and 4 and 12 weeks after vaccination

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2014
• Primary Completion (Actual): July 29, 2021
• Study Completion (Actual): July 29, 2021

Study Registration Dates

• First Submitted: January 28, 2014
• First Submitted That Met QC Criteria: January 28, 2014
• First Posted (Estimate): January 30, 2014

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: June 15, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Arthritis; Joint Diseases; Anti-inflammatory Agents; Musculoskeletal Disease; Antirheumatic agents
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Upadacitinib
• Other Study ID Numbers: M13-538; 2013-003530-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing, please refer to the link below.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No