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

Rheumatoid Arthritis Clinical Trial

— BALANCE-EXTEND  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02049138
• Other study ID #: M13-538
• Secondary ID: 2013-003530-33
• Status: Completed
• Phase: Phase 2
• Start date: January 24, 2014
• Est. completion date: July 29, 2021

Study information

• Verified date: June 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 493
• Est. completion date: July 29, 2021
• Est. primary completion date: July 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Upadacitinib
Tablet taken orally

Biological:
• Pneumococcal 13-valent conjugate vaccine (PCV-13)
Administered by intramuscular injection

Locations

Country	Name	City	State
Belgium	ReumaClinic Genk-Hasselt /ID# 137775	Genk
Belgium	UCL Saint-Luc /ID# 139348	Woluwe-Saint-Lambert	Bruxelles-Capitale
Bulgaria	Duplicate_MHAT Kaspela /ID# 136212	Plovdiv
Bulgaria	MHAT Trimontsium /ID# 135328	Plovdiv
Bulgaria	UHMAT Palmed Plovdiv /ID# 135355	Plovdiv
Bulgaria	Diagnostic Consultative Center /ID# 136736	Sofia
Bulgaria	UMHAT Sveti Ivan Rilski /ID# 135678	Sofia
Bulgaria	UMHAT Sveti Ivan Rilski /ID# 136210	Sofia
Bulgaria	Diagnostic consultative center Equita /ID# 136209	Varna
Chile	Corporacion de Beneficiencia Osorno /ID# 136189	Osorno	Los Lagos
Chile	Quantum Research /ID# 136188	Puerto Varas	Los Lagos
Czechia	Duplicate_Artroscan s.r.o. /ID# 139347	Ostrava
Czechia	L.K.N. Arthrocentrum, s.r.o /ID# 128782	Petrkovice
Czechia	Revmatologicka ambulance - MUDr. Zuzana Urbanova /ID# 137776	Praha
Czechia	Revmatologicky ustav v Praze /ID# 137937	Praha
Czechia	Revmatologie Bruntal, s.r.o /ID# 137782	Prostejov
Hungary	Orszagos Reumatologiai es Fizioterapias Intezet /ID# 128785	Budapest
Hungary	Qualiclinic Kft. /ID# 134170	Budapest	Pest
Hungary	Szent Margit Szakrendelo /ID# 136676	Budapest
Hungary	MAV Korhaz ess Rendelointezet /ID# 139971	Szolnok
Hungary	Veszprem Megyei Csolnoky Ferenc Korhaz /ID# 128784	Veszprem
Israel	Barzilai Medical Center /ID# 140199	Ashkelon
Israel	The Chaim Sheba Medical Center /ID# 139295	Ramat Gan	Tel-Aviv
Latvia	M & M Centrs LTD /ID# 132439	Adazi
Latvia	Arija's Ancane's Family Doctor Practice /ID# 132437	Baldone
Latvia	Clinic ORTO /ID# 132438	Riga
Mexico	Clinstile, S.A. de C.V. /ID# 137075	Cuauhtemoc	Ciudad De Mexico
Mexico	Cliditer SA de CV /ID# 136876	Mexico City
Mexico	Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 137307	Mexico City
New Zealand	Waikato Hospital /ID# 131908	Hamilton	Waikato
New Zealand	Porter Rheumatology Ltd /ID# 133983	Nelson
New Zealand	Timaru Medical Specialists Ltd /ID# 131909	Timaru	Canterbury
Poland	Gabinet Internistyczno-Reumatologiczny /ID# 135876	Bialystok	Podlaskie
Poland	Ambulatorium Sp. z o.o /ID# 138074	Elblag	Warminsko-mazurskie
Poland	Centrum Medyczne Pratia Gdynia /ID# 137362	Gdynia	Pomorskie
Poland	Pratia MCM Krakow /ID# 134749	Krakow	Malopolskie
Poland	Duplicate_REUMED Filia nr 2 /ID# 128839	Lublin
Poland	NZOZ Lecznica MAK-MED s.c. /ID# 128838	Nadarzyn	Mazowieckie
Poland	Twoja Przychodnia Centrum Medyczne /ID# 128840	Nowa Sol	Lubuskie
Poland	Medicome sp. z o.o. /ID# 137397	Oswiecim	Mazowieckie
Poland	Prywatna Praktyka Lekarska /ID# 128837	Poznan	Wielkopolskie
Poland	Centrum Medyczne Amed Warszawa Zoliborz /ID# 128835	Warsaw	Mazowieckie
Poland	Centrum Medyczne Pratia Warszawa /ID# 136650	Warsaw	Mazowieckie
Poland	Centrum Medyczne Reuma Park w Warszawie /ID# 140198	Warsaw	Mazowieckie
Poland	NBR Polska /ID# 136208	Warszawa	Mazowieckie
Poland	Reum-Medica S.C. /ID# 128841	Wroclaw	Dolnoslaskie
Puerto Rico	Dr. Ramon L. Ortega-Colon, MD /ID# 128760	Carolina
Puerto Rico	GCM Medical Group PSC - Hato Rey /ID# 128759	San Juan
Puerto Rico	Mindful Medical Research /ID# 136211	San Juan
Russian Federation	Kazan State Medical University /ID# 136734	Kazan	Tatarstan, Respublika
Russian Federation	St. Petersburg Research Institute of Emergency Medicine n.?. I. I. Dzhanelidze /ID# 136652	Sankt-Peterburg
Russian Federation	Tver Regional Clinical Hospital /ID# 137576	Tver	Tverskaya Oblast
Slovakia	MEDMAN s.r.o. /ID# 136649	Martin
Slovakia	Poliklinika Senica n.o. /ID# 134728	Senica
South Africa	Dr MJ Prins /ID# 138540	Cape Town	Western Cape
South Africa	Winelands Medical Research Centre /ID# 134669	Stellenbosch	Western Cape
Spain	Hospital Universitario A Coruna - CHUAC /ID# 128846	A Coruna
Spain	Hospital CIMA Sanitas /ID# 128849	Barcelona
Spain	Hospital General Universitario de Elche /ID# 128851	Elche	Alicante
Spain	Hospital Clinico Universitario San Carlos /ID# 128852	Madrid
Spain	Hospital Regional de Malaga /ID# 128847	Málaga	Malaga
Spain	Hospital Infanta Sofia /ID# 136653	San Sebastián de Los Reyes	Madrid
Spain	Clinica Gaias /ID# 133868	Santiago de Compostela	A Coruna
Spain	Hospital QuironSalud Infanta Luisa /ID# 135689	Sevilla
Spain	Hospital Universitario Virgen de Valme /ID# 134668	Sevilla
Spain	Hospital Universitario Virgen Macarena /ID# 128853	Sevilla
Ukraine	NSC Strazhesko Ist Cardiology /ID# 137330	Kiev
Ukraine	Municipal Non-profit Institution Kyiv City Clinical Hospital No. 3 of the Exec /ID# 137334	Kyiv
United Kingdom	West Suffolk Hospital /ID# 128858	Bury St Edmunds	Suffolk
United Kingdom	Duplicate_Leeds Teaching Hospitals NHS Trust /ID# 141308	Leeds
United Kingdom	Barts Health NHS Trust /ID# 135683	London	London, City Of
United Kingdom	Warrington and Halton Hospitals NHS Foundation Trust /ID# 137514	Warrington	Cheshire West And Chester
United States	Austin Rheumatology Research /ID# 124083	Austin	Texas
United States	Arthritis & Rheumatic Disease Specialties /ID# 135910	Aventura	Florida
United States	Accurate Clinical Management /ID# 128751	Baytown	Texas
United States	Duplicate_East Penn Rheumatology Assoc /ID# 135920	Bethlehem	Pennsylvania
United States	Rheumatology Associates of South Florida (RASF) - Clinical Research /ID# 124082	Boca Raton	Florida
United States	New England Research Associates, LLC /ID# 124085	Bridgeport	Connecticut
United States	DJL Clinical Research, PLLC /ID# 131936	Charlotte	North Carolina
United States	Cincinnati Rheumatic Disease Study Group, Inc. /ID# 135921	Cincinnati	Ohio
United States	Mountain State Clinical Research /ID# 124088	Clarksburg	West Virginia
United States	Summit Medical Group /ID# 124076	Clifton	New Jersey
United States	Omega Research Maitland, LLC /ID# 124094	DeBary	Florida
United States	Denver Arthritis Clinic /ID# 135901	Denver	Colorado
United States	Altoona Ctr Clinical Res /ID# 124089	Duncansville	Pennsylvania
United States	Aurora Rheumatology and Immunotherapy Center /ID# 135922	Franklin	Wisconsin
United States	Arthritis and Osteoporosis Associates /ID# 135907	Freehold	New Jersey
United States	Klein and Associates MD - Hagerstown /ID# 124086	Hagerstown	Maryland
United States	C.V. Mehta MD, Med Corporation /ID# 124092	Hemet	California
United States	Accurate Clinical Management /ID# 128752	Houston	Texas
United States	Accurate Clinical Research /ID# 128753	Houston	Texas
United States	Accurate Clinical Research /ID# 128754	Houston	Texas
United States	Baylor College of Medicine - Baylor Medical Center /ID# 135905	Houston	Texas
United States	Houston Institute for Clin Res /ID# 135912	Houston	Texas
United States	Rheum Assoc of North Alabama /ID# 135926	Huntsville	Alabama
United States	University of Florida /ID# 124087	Jacksonville	Florida
United States	Moores Cancer Center at UC San Diego /ID# 128747	La Jolla	California
United States	June DO, PC /ID# 124081	Lansing	Michigan
United States	Arthritis and Osteo Assoc /ID# 132280	Las Cruces	New Mexico
United States	North Georgia Rheumatology Group /ID# 128746	Lawrenceville	Georgia
United States	Dr. Ramesh Gupta /ID# 128744	Memphis	Tennessee
United States	SW Rheumatology Res. LLC /ID# 135927	Mesquite	Texas
United States	Suncoast Research Group /ID# 137774	Miami	Florida
United States	Health Research of Oklahoma /ID# 135904	Oklahoma City	Oklahoma
United States	Omega Research Maitland, LLC /ID# 137398	Orlando	Florida
United States	Millennium Research /ID# 135917	Ormond Beach	Florida
United States	Kansas City Internal Medicine /ID# 135916	Overland Park	Kansas
United States	Desert Medical Advances - Palm Desert /ID# 135911	Palm Desert	California
United States	Arthritis Center, Inc. /ID# 124090	Palm Harbor	Florida
United States	AZ Arthritis and Rheumotology Research, PLLC /ID# 135902	Phoenix	Arizona
United States	AZ Arthritis and Rheumotology Research, PLLC /ID# 135931	Phoenix	Arizona
United States	IRIS Research and Development, LLC /ID# 140362	Plantation	Florida
United States	Orrin Troum, M.D. and Medical /ID# 135933	Santa Monica	California
United States	Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 124080	Summerville	South Carolina
United States	Duplicate_Robin K. Dore MD, Inc /ID# 135906	Tustin	California
United States	Inland Rheum Clin Trials Inc. /ID# 136716	Upland	California
United States	STAT Research, Inc. /ID# 134906	Vandalia	Ohio
United States	Lovelace Scientific Resources /ID# 128745	Venice	Florida
United States	Duplicate_Desert Valley Medical Group /ID# 135932	Victorville	California
United States	Arthritis Rheumatic and Back Disease Associates. P.A. /ID# 135913	Voorhees	New Jersey
United States	The Center for Rheumatology and Bone Research /ID# 124077	Wheaton	Maryland
United States	PRN Professional Research Network of Kansas, LLC /ID# 124091	Wichita	Kansas
United States	Clinical Pharmacology Study Group /ID# 124079	Worcester	Massachusetts
United States	Emkey Arthritis and Osteoporosis Clinic /ID# 135908	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	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
Primary	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).	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
Primary	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).	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Related Info.