Rheumatoid ArthritisPhase 2BALANCE-EXTENDNCT02049138
An Open-label Extension Study Evaluating the Safety and Efficacy of Upadacitinib (ABT-494) in Adults With Rheumatoid Arthritis
A Phase 2 study testing Upadacitinib and Pneumococcal 13-valent conjugate vaccine (PCV-13) in people with Rheumatoid Arthritis, run by AbbVie at 124 sites in 18 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Upadacitinib and Pneumococcal 13-valent conjugate vaccine (PCV-13)
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 493 participants
- Where
- 124 sitesin 18 countries
- Study dates
- 24 Jan 2014to 29 Jul 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
124 sites in 18 countries.
124 sites in 18 countries
United States52 sites
Austin Rheumatology Research /ID# 124083
Austin, Texas, 78705
Arthritis & Rheumatic Disease Specialties /ID# 135910
Aventura, Florida, 33180
Accurate Clinical Management /ID# 128751
Baytown, Texas, 77521
Duplicate_East Penn Rheumatology Assoc /ID# 135920
Bethlehem, Pennsylvania, 18015
Rheumatology Associates of South Florida (RASF) - Clinical Research /ID# 124082
Boca Raton, Florida, 33486
New England Research Associates, LLC /ID# 124085
Bridgeport, Connecticut, 06606-1827
DJL Clinical Research, PLLC /ID# 131936
Charlotte, North Carolina, 28210-8508
Cincinnati Rheumatic Disease Study Group, Inc. /ID# 135921
Cincinnati, Ohio, 45242-4468
Mountain State Clinical Research /ID# 124088
Clarksburg, West Virginia, 26301
Summit Medical Group /ID# 124076
Clifton, New Jersey, 07012-1647
Omega Research Maitland, LLC /ID# 124094
DeBary, Florida, 32713-2260
Denver Arthritis Clinic /ID# 135901
Denver, Colorado, 80230
Altoona Ctr Clinical Res /ID# 124089
Duncansville, Pennsylvania, 16635
Aurora Rheumatology and Immunotherapy Center /ID# 135922
Franklin, Wisconsin, 53132
Arthritis and Osteoporosis Associates /ID# 135907
Freehold, New Jersey, 07728-8307
Klein and Associates MD - Hagerstown /ID# 124086
Hagerstown, Maryland, 21742
C.V. Mehta MD, Med Corporation /ID# 124092
Hemet, California, 92543
Accurate Clinical Management /ID# 128752
Houston, Texas, 77004
Baylor College of Medicine - Baylor Medical Center /ID# 135905
Houston, Texas, 77030-3411
Houston Institute for Clin Res /ID# 135912
Houston, Texas, 77074
Accurate Clinical Research /ID# 128753
Houston, Texas, 77089
Accurate Clinical Research /ID# 128754
Houston, Texas, 77089
Rheum Assoc of North Alabama /ID# 135926
Huntsville, Alabama, 35801
University of Florida /ID# 124087
Jacksonville, Florida, 32209
Moores Cancer Center at UC San Diego /ID# 128747
La Jolla, California, 92093
June DO, PC /ID# 124081
Lansing, Michigan, 48910
Arthritis and Osteo Assoc /ID# 132280
Las Cruces, New Mexico, 88011
North Georgia Rheumatology Group /ID# 128746
Lawrenceville, Georgia, 30045
Dr. Ramesh Gupta /ID# 128744
Memphis, Tennessee, 38119
SW Rheumatology Res. LLC /ID# 135927
Mesquite, Texas, 75150
Suncoast Research Group /ID# 137774
Miami, Florida, 33135
Health Research of Oklahoma /ID# 135904
Oklahoma City, Oklahoma, 73103-2400
Omega Research Maitland, LLC /ID# 137398
Orlando, Florida, 32808
Millennium Research /ID# 135917
Ormond Beach, Florida, 32174
Kansas City Internal Medicine /ID# 135916
Overland Park, Kansas, 66209
Desert Medical Advances - Palm Desert /ID# 135911
Palm Desert, California, 92260
Arthritis Center, Inc. /ID# 124090
Palm Harbor, Florida, 34684
AZ Arthritis and Rheumotology Research, PLLC /ID# 135902
Phoenix, Arizona, 85032-9306
AZ Arthritis and Rheumotology Research, PLLC /ID# 135931
Phoenix, Arizona, 85032-9306
IRIS Research and Development, LLC /ID# 140362
Plantation, Florida, 33324
Orrin Troum, M.D. and Medical /ID# 135933
Santa Monica, California, 90404
Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 124080
Summerville, South Carolina, 29486-7887
Duplicate_Robin K. Dore MD, Inc /ID# 135906
Tustin, California, 92780
Inland Rheum Clin Trials Inc. /ID# 136716
Upland, California, 91786
STAT Research, Inc. /ID# 134906
Vandalia, Ohio, 45377-9464
Lovelace Scientific Resources /ID# 128745
Venice, Florida, 34292
Duplicate_Desert Valley Medical Group /ID# 135932
Victorville, California, 92395
Arthritis Rheumatic and Back Disease Associates. P.A. /ID# 135913
Voorhees Township, New Jersey, 08043
The Center for Rheumatology and Bone Research /ID# 124077
Wheaton, Maryland, 20902
PRN Professional Research Network of Kansas, LLC /ID# 124091
Wichita, Kansas, 67205
Clinical Pharmacology Study Group /ID# 124079
Worcester, Massachusetts, 01605
Emkey Arthritis and Osteoporosis Clinic /ID# 135908
Wyomissing, Pennsylvania, 19610
Poland14 sites
Gabinet Internistyczno-Reumatologiczny /ID# 135876
Bialystok, Podlaskie Voivodeship, 15-077
Ambulatorium Sp. z o.o /ID# 138074
Elblag, Warmian-Masurian Voivodeship, 82-300
Centrum Medyczne Pratia Gdynia /ID# 137362
Gdynia, Pomeranian Voivodeship, 81-338
Pratia MCM Krakow /ID# 134749
Krakow, Lesser Poland Voivodeship, 30-510
Duplicate_REUMED Filia nr 2 /ID# 128839
Lublin, 20-582
NZOZ Lecznica MAK-MED s.c. /ID# 128838
Nadarzyn, Masovian Voivodeship, 05-830
Twoja Przychodnia Centrum Medyczne /ID# 128840
Nowa Sól, Lubusz Voivodeship, 67-100
Medicome sp. z o.o. /ID# 137397
Oswiecim, Masovian Voivodeship, 32-600
Prywatna Praktyka Lekarska /ID# 128837
Poznan, Greater Poland Voivodeship, 61-397
NBR Polska /ID# 136208
Warsaw, Masovian Voivodeship, 00-465
Centrum Medyczne Amed Warszawa Zoliborz /ID# 128835
Warsaw, Masovian Voivodeship, 01-518
Centrum Medyczne Pratia Warszawa /ID# 136650
Warsaw, Masovian Voivodeship, 01-868
Centrum Medyczne Reuma Park w Warszawie /ID# 140198
Warsaw, Masovian Voivodeship, 02-691
Reum-Medica S.C. /ID# 128841
Wroclaw, Lower Silesian Voivodeship, 50-244
Spain10 sites
Hospital Universitario A Coruna - CHUAC /ID# 128846
A Coruña, 15006
Hospital CIMA Sanitas /ID# 128849
Barcelona, 08034
Hospital General Universitario de Elche /ID# 128851
Elche, Alicante, 03203
Hospital Clinico Universitario San Carlos /ID# 128852
Madrid, 28040
Hospital Regional de Malaga /ID# 128847
Málaga, Malaga, 29010
Hospital Infanta Sofia /ID# 136653
San Sebastián de los Reyes, Madrid, 28702
Clinica Gaias /ID# 133868
Santiago de Compostela, A Coruna, 15702
Hospital Universitario Virgen Macarena /ID# 128853
Seville, 41009
Hospital QuironSalud Infanta Luisa /ID# 135689
Seville, 41010
Hospital Universitario Virgen de Valme /ID# 134668
Seville, 41014
Bulgaria7 sites
MHAT Trimontsium /ID# 135328
Plovdiv, 4000
Duplicate_MHAT Kaspela /ID# 136212
Plovdiv, 4001
UHMAT Palmed Plovdiv /ID# 135355
Plovdiv, 4002
UMHAT Sveti Ivan Rilski /ID# 135678
Sofia, 1431
UMHAT Sveti Ivan Rilski /ID# 136210
Sofia, 1431
Diagnostic Consultative Center /ID# 136736
Sofia, 1612
Diagnostic consultative center Equita /ID# 136209
Varna, 9000
Czechia5 sites
Duplicate_Artroscan s.r.o. /ID# 139347
Ostrava, 722 00
L.K.N. Arthrocentrum, s.r.o /ID# 128782
Petřkovice, 725 29
Revmatologicky ustav v Praze /ID# 137937
Prague, 128 00
Revmatologicka ambulance - MUDr. Zuzana Urbanova /ID# 137776
Prague, 140 00
Revmatologie Bruntal, s.r.o /ID# 137782
Prostějov, 796 01
Hungary5 sites
Qualiclinic Kft. /ID# 134170
Budapest, Pest County, 1036
Orszagos Reumatologiai es Fizioterapias Intezet /ID# 128785
Budapest, 1023
Szent Margit Szakrendelo /ID# 136676
Budapest, 1032
MAV Korhaz ess Rendelointezet /ID# 139971
Szolnok, 5000
Veszprem Megyei Csolnoky Ferenc Korhaz /ID# 128784
Veszprém, 8200
United Kingdom4 sites
West Suffolk Hospital /ID# 128858
Bury St Edmunds, Suffolk, IP33 2QZ
Duplicate_Leeds Teaching Hospitals NHS Trust /ID# 141308
Leeds, LS9 7TF
Barts Health NHS Trust /ID# 135683
London, London, City of, E1 2ES
Warrington and Halton Hospitals NHS Foundation Trust /ID# 137514
Warrington, Cheshire West And Chester, WA5 1QG
Latvia3 sites
M & M Centrs LTD /ID# 132439
Adazi, LV-2164
Arija's Ancane's Family Doctor Practice /ID# 132437
Baldone, LV-2125
Clinic ORTO /ID# 132438
Riga, LV-1005
Mexico3 sites
Clinstile, S.A. de C.V. /ID# 137075
Cuauhtémoc, Mexico City, 20313
Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 137307
Mexico City, 06090
Cliditer SA de CV /ID# 136876
Mexico City, 06700
New Zealand3 sites
Waikato Hospital /ID# 131908
Hamilton, Waikato Region, 3240
Porter Rheumatology Ltd /ID# 133983
Nelson, 7010
Timaru Medical Specialists Ltd /ID# 131909
Timaru, Canterbury, 7910
Puerto Rico3 sites
Dr. Ramon L. Ortega-Colon, MD /ID# 128760
Carolina, 00983
GCM Medical Group PSC - Hato Rey /ID# 128759
San Juan, 00917-3104
Mindful Medical Research /ID# 136211
San Juan, 00918-3756
Russia3 sites
Kazan State Medical University /ID# 136734
Kazan', Tatarstan, Respublika, 420012
St. Petersburg Research Institute of Emergency Medicine n.а. I. I. Dzhanelidze /ID# 136652
Saint Petersburg, 192242
Tver Regional Clinical Hospital /ID# 137576
Tver', Tver Oblast, 170036
Belgium2 sites
ReumaClinic Genk-Hasselt /ID# 137775
Genk, 3600
UCL Saint-Luc /ID# 139348
Woluwe-Saint-Lambert, Brussels Capital, 1200
Chile2 sites
Corporacion de Beneficiencia Osorno /ID# 136189
Osorno, Los Lagos Region, 1710216
Quantum Research /ID# 136188
Puerto Varas, Los Lagos Region, 5550170
Israel2 sites
Barzilai Medical Center /ID# 140199
Ashkelon, 7830604
The Chaim Sheba Medical Center /ID# 139295
Ramat Gan, Tel Aviv, 5265601
Slovakia2 sites
MEDMAN s.r.o. /ID# 136649
Martin, 036 01
Poliklinika Senica n.o. /ID# 134728
Senica, 905 01
South Africa2 sites
Dr MJ Prins /ID# 138540
Cape Town, Western Cape, 7500
Winelands Medical Research Centre /ID# 134669
Stellenbosch, Western Cape, 7600
Ukraine2 sites
NSC Strazhesko Ist Cardiology /ID# 137330
Kiev, 03680
Municipal Non-profit Institution Kyiv City Clinical Hospital No. 3 of the Exec /ID# 137334
Kyiv, 02125
About this study
Official title: 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.
Read the 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
- Being tested
- Upadacitinib, Pneumococcal 13-valent conjugate vaccine (PCV-13)
- Keywords
- Musculoskeletal Disease, Arthritis, Joint Diseases, Anti-inflammatory Agents, Antirheumatic agents
- Medical subject headings
- Arthritis, Rheumatoid, Musculoskeletal Diseases, Arthritis, Joint Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UpadacitinibDrug
Also called ABT-494, RINVOQ®
Tablet taken orally
Pneumococcal 13-valent conjugate vaccine (PCV-13)Biological
Also called Prevnar 13®
Administered by intramuscular injection
| Study group | Role | What they receive |
|---|---|---|
| Upadacitinib | Experimental | 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). Receives: Drug: Upadacitinib; Biological: Pneumococcal 13-valent conjugate vaccine (PCV-13) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: 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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: 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 activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Measured: 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).
Measured: 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 outcomes (22)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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
Measured: 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.
Measured: 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."
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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
Measured: Vaccination Baseline and 4 and 12 weeks after vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2014 (estimated)
- Study start24 Jan 2014
- Primary completion29 Jul 2021
- Study completion29 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 493 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- ABBVIE INC., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02049138
- Sponsor's protocol ID
- M13-538
- Other IDs
- 2013-003530-33
- Acronym
- BALANCE-EXTEND
- Status last verified
- Jun 2022
- First submitted
- 28 Jan 2014
- Last updated
- 12 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 37723577Kivitz 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.
PubMed 37199884Winthrop 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.
PubMed 35246470
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02049138
- Acronym / sponsor ID
- BALANCE-EXTEND / M13-538
- Conditions
- Rheumatoid Arthritis
- Keywords
- Musculoskeletal Disease, Arthritis, Joint Diseases, Anti-inflammatory Agents, Antirheumatic agents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 493 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- 24 Jan 2014 (actual)
- Primary completion
- 29 Jul 2021 (actual)
- Study completion
- 29 Jul 2021 (actual)
- First posted
- 30 Jan 2014 (estimated)
- Results
- Posted 12 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Upadacitinib | Experimental | Drug: Upadacitinib, Biological: Pneumococcal 13-valent conjugate vaccine (PCV-13)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). |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
- Must currently be enrolled in the main study.
Key exclusion criteria (22 listed)
- 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:
- Enrollment in another interventional clinical study while participating in this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UpadacitinibAlso: ABT-494, RINVOQ®Tablet taken orally | Drug | Upadacitinib |
| Pneumococcal 13-valent conjugate vaccine (PCV-13)Also: Prevnar 13®Administered by intramuscular injection | Biological | Upadacitinib |
Primary outcome
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Over Time
Time frame: 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
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).
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response Over Time
Time frame: 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
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria: 1. ≥ 50% improvement in 68-tender joint count; 2. ≥ 50% improvement in 66-swollen joint count; and 3. ≥ 50% 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).
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response Over Time
Time frame: 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
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria: 1. ≥ 70% improvement in 68-tender joint count; 2. ≥ 70% improvement in 66-swollen joint count; and 3. ≥ 70% 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).
Percentage of Participants With Satisfactory Humoral Response to PCV-13 Four Weeks After Vaccination
Time frame: Vaccination Baseline (defined as the last non-missing observation on or before the date of receiving PCV-13 vaccination) and 4 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).
22 secondary outcomes
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Vaccination Baseline and 4 and 12 weeks after vaccination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37723577Baraliakos 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.
- Derived from this study: PubMed 37199884Kivitz 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.
- Derived from this study: PubMed 35246470Winthrop 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.
- Related Info.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ABBVIE INC. study director
AbbVie
124 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Upadacitinib and Pneumococcal 13-valent conjugate vaccine (PCV-13) in people with Rheumatoid Arthritis, run by AbbVie at 124 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 124 sites in United States, Poland, Spain, Bulgaria, Czechia and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Over Time (time frame: 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02049138, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2022.