A Study to Investigate the Safety and Efficacy of ABBV-105 Alone or in Combination With Upadacitinib (ABBV-599 Combination) in Participants With Active Rheumatoid Arthritis

Rheumatoid Arthritis (RA) Clinical Trial

Official title:

Rheumatoid Arthritis: A Phase 2 Study to Investigate the Safety and Efficacy of ABBV-105 Given Alone or in Combination With Upadacitinib (ABBV-599 Combination) With a Background of Conventional Synthetic DMARDs in Subjects With Active Rheumatoid Arthritis With Inadequate Response or Intolerance to Biologic DMARDs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03682705
• Other study ID #: M16-063
• Secondary ID: 2018-000666-10
• Status: Completed
• Phase: Phase 2
• Start date: October 8, 2018
• Est. completion date: March 26, 2020

Study information

• Verified date: April 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was a phase 2 study to evaluate the safety and efficacy of elsubrutinib (ELS) and ABBV-599 (ELS plus upadacitinib [UPA]) vs placebo on a background of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for the treatment of signs and symptoms of rheumatoid arthritis (RA) at 12 weeks in biological disease-modifying anti-rheumatic drugs (bDMARD)-inadequate response (bDMARD-IR) or bDMARD-intolerant participants with moderately to severely active RA and to define optimal dose for further development.

Description:

This was a 12-week, randomized, double-blind, parallel-group, Phase 2, dose exploratory, multicenter study. Participants who met eligibility criteria were randomized in a 3:2:2:2:2:1 ratio to 1 of 6 treatment groups: ABBV-599 [UPA 15 mg/ELS 60 mg]); ELS 60 mg/UPA placebo; ELS 20 mg/UPA placebo; ELS 5 mg/UPA placebo; UPA 15 mg/ELS placebo; and ELS placebo/UPA placebo. The study included a 35-day maximum screening period and a 12-week treatment period with 30-day follow-up.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 242
• Est. completion date: March 26, 2020
• Est. primary completion date: March 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of rheumatoid arthritis (RA) for = 3 months based on the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA
• Participant meets the following minimum disease activity criteria:
• = 6 swollen joints (based on 66 joint counts) and = 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits
• High-sensitivity C-reactive protein (hsCRP) = 3 mg/L (central lab) at Screening Visit
• Participants must have been treated for = 3 months with = 1 biologic disease-modifying anti-rheumatic drug (bDMARD) therapy but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration
• Participants must have been receiving conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy = 3 months and on a stable dose for = 4 weeks prior to the first dose of study drug
• Participants must have discontinued all bDMARDs prior to the first dose of study drug

Exclusion Criteria:

• Participant has prior exposure to any Janus Kinase (JAK) inhibitor for greater than 2 weeks (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib). A washout period of = 30 days is required for any JAK inhibitor prior to the first dose of study drug.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis (RA)

Intervention

Drug:
• Elsubrutinib
Elsubrutinib capsule will be administered orally.
• Upadacitinib
Upadacitinib tablet will be administered orally.
• Placebo for elsubrutinib
Placebo capsule for elsubrutinib will be administered orally.
• Placebo for upadacitinib
Placebo tablet for upadacitinib will be administered orally.

Locations

Country	Name	City	State
Belgium	CUB Hospital Erasme /ID# 201965	Brussels	Bruxelles-Capitale
Belgium	UZ Ghent /ID# 201757	Ghent	Oost-Vlaanderen
Belgium	UZ Leuven /ID# 201927	Leuven
Belgium	Cliniques Universitaires Saint Luc /ID# 201756	Woluwe-Saint-Lambert	Bruxelles-Capitale
Canada	Rheumatology Research Assoc /ID# 207299	Edmonton	Alberta
Canada	Credit Valley Rheumatology /ID# 202124	Mississauga	Ontario
Canada	Dr. Latha Naik /ID# 212972	Saskatoon	Saskatchewan
Canada	Mount Sinai Hosp.-Toronto /ID# 202652	Toronto	Ontario
Canada	CIADS Research Co Ltd /ID# 202125	Winnipeg	Manitoba
Canada	Manitoba Clinic /ID# 202126	Winnipeg	Manitoba
Czechia	Revmatolog s.r.o. /ID# 202610	Jihlava 1	Jihlava
Czechia	Revmatologie MUDr. Klara Sirova /ID# 205185	Ostrava
Czechia	CCR Czech a.s /ID# 202144	Pardubice
Czechia	Revmatologicky ustav Praha /ID# 202142	Prague 2	Praha 2
Hungary	Revita Reumatologiai Rendelo /ID# 202438	Budapest
Hungary	CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 202439	Miskolc	Borsod-Abauj-Zemplen
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak & Egyetemi Oktatokorhaz /ID# 202441	Nyíregyháza	Szabolcs-Szatmar-Bereg
Hungary	CMED Rehabilitacios es Diagnosztikai Kozpont /ID# 205804	Szekesfehervar
Hungary	Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 202437	Veszprem
Poland	ClinicMed Daniluk, Nowak Sp.j. /ID# 212576	Bialystok	Podlaskie
Poland	Malopolskie Centrum Kliniczne /ID# 206473	Cracow	Malopolskie
Poland	McBk Sc /Id# 212575	Grodzisk Mazowiecki	Mazowieckie
Poland	NBR Polska /ID# 206476	Warsaw	Mazowieckie
Poland	Reumatika - Centrum Reumatologii NZOZ /ID# 206472	Warsaw
Puerto Rico	GCM Medical Group, PSC /ID# 167983	San Juan
Spain	Hospital Universitario A Coruña - CHUAC /ID# 202140	A Coruña	A Coruna
Spain	Hospital Clinic /ID# 206575	Barcelona
Spain	Hospital Santa Creu i Sant Pau /ID# 206535	Barcelona
Spain	Hospital Universitario Basurto /ID# 206462	Bilbao
Spain	Hospital Universitario Virgen de las Nieves /ID# 209705	Granada
Spain	Hospital Clinico Universitario San Carlos /ID# 202135	Madrid
Spain	Hospital Regional de Malaga /ID# 202137	Málaga	Malaga
Spain	Hospital Unversitario Marques de Valdecilla /ID# 202133	Santander	Cantabria
Spain	Hospital Universitario y Politecnico La Fe /ID# 202139	Valencia
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 201976	Newcastle Upon Tyne
United Kingdom	University of Oxford /ID# 201974	Oxford
United Kingdom	Warrington and Halton Teaching Hosp NHS Foundation Trust /ID# 206002	Warrington
United States	Amarillo Ctr for Clin Research /ID# 200484	Amarillo	Texas
United States	Tekton Research, Inc. /ID# 167475	Austin	Texas
United States	Rheumatology and Pulmonary cli /ID# 170863	Beckley	West Virginia
United States	New Horizons Clinical Research /ID# 170862	Blue Ash	Ohio
United States	Western Washington Arthritis C /ID# 205821	Bothell	Washington
United States	Bay Area Arthritis and Osteo /ID# 208111	Brandon	Florida
United States	Trinity Universal Res Assoc /ID# 209252	Carrollton	Texas
United States	DJL Clinical Research, PLLC /ID# 167374	Charlotte	North Carolina
United States	Great Lakes Clinical Trials /ID# 167471	Chicago	Illinois
United States	Clinical Res of West FL, Inc. /ID# 167462	Clearwater	Florida
United States	Arth and Osteo Clin Brazo Valley /ID# 209401	College Station	Texas
United States	Metroplex Clinical Research /ID# 167458	Dallas	Texas
United States	Omega Research Maitland, LLC /ID# 167376	DeBary	Florida
United States	EmergeOrtho, P.A. /ID# 209154	Durham	North Carolina
United States	Riverside Clinical Research /ID# 167982	Edgewater	Florida
United States	Aurora Rheumatology and Immunotherapy Center /ID# 167385	Franklin	Wisconsin
United States	St. Joseph Heritage Healthcare /ID# 167379	Fullerton	California
United States	Arthritis Associates /ID# 209075	Hattiesburg	Mississippi
United States	Accurate Clinical Research /ID# 207059	Houston	Texas
United States	Rheumatic Disease Clin Res Ctr /ID# 167474	Houston	Texas
United States	Rheumatology Clinic of Houston /ID# 203689	Houston	Texas
United States	Rheum Assoc of North Alabama /ID# 167382	Huntsville	Alabama
United States	Institute of Arthritis Researc /ID# 170694	Idaho Falls	Idaho
United States	West Tennessee Research Inst /ID# 167366	Jackson	Tennessee
United States	Purushotham, Akther & Roshan K /ID# 168121	La Mesa	California
United States	Beals Instititute /ID# 170658	Lansing	Michigan
United States	June DO, PC /ID# 170670	Lansing	Michigan
United States	Arthritis and Osteo Assoc /ID# 167443	Las Cruces	New Mexico
United States	Dhmc /Id# 167476	Lebanon	New Hampshire
United States	Cape Fear Arthritis Care /ID# 167413	Leland	North Carolina
United States	Rheumatology Consultants of De /ID# 208238	Lewes	Delaware
United States	Physician Research Collaboration, LLC /ID# 200480	Lincoln	Nebraska
United States	Valerius Medical Group /ID# 168123	Los Alamitos	California
United States	West Texas Clinical Research /ID# 205732	Lubbock	Texas
United States	Mansfield Health Center /ID# 167372	Mansfield	Massachusetts
United States	Marietta Memorial Hospital /ID# 210968	Marietta	Ohio
United States	AZ Arthritis & Rheum Research /ID# 167446	Mesa	Arizona
United States	SW Rheumatology Res. LLC /ID# 167383	Mesquite	Texas
United States	Kendall South Medical Center, Inc. /ID# 206857	Miami	Florida
United States	Lakes Research, LLC /ID# 170660	Miami	Florida
United States	The Arthritis & Diabetes Clinic, Inc. /ID# 170682	Monroe	Louisiana
United States	Medallion Clinical Research Institute, LLC /ID# 201710	Naples	Florida
United States	Nashville Arthritis and Rheumatology /ID# 206699	Nashville	Tennessee
United States	Tidewater Physicians Medical Center /ID# 210884	Newport News	Virginia
United States	Health Research of Oklahoma /ID# 167370	Oklahoma City	Oklahoma
United States	HMD Research LLC /ID# 208381	Orlando	Florida
United States	Rheum Assoc of Central FL /ID# 170858	Orlando	Florida
United States	International Medical Research - Ormond /ID# 170864	Ormond Beach	Florida
United States	Millennium Research /ID# 167453	Ormond Beach	Florida
United States	Arthritis Center, Inc. /ID# 170695	Palm Harbor	Florida
United States	SunValley Arthritis Center, Lt /ID# 213073	Peoria	Arizona
United States	AZ Arthritis and Rheum Researc /ID# 167448	Phoenix	Arizona
United States	Trinity Universal Research Association /ID# 209253	Plano	Texas
United States	Integral Rheumatology & Immunology Specialists /ID# 206724	Plantation	Florida
United States	Sierra Rheumatology /ID# 167976	Roseville	California
United States	Clayton Medical Associates dba Saint Louis Rheumatology /ID# 170650	Saint Louis	Missouri
United States	BayCare Medical Group /ID# 170860	Saint Petersburg	Florida
United States	St. Anthony Comprehensive Rese /ID# 170668	Saint Petersburg	Florida
United States	Accurate Clinical Management /ID# 200481	San Antonio	Texas
United States	Sun Research Institute /ID# 170667	San Antonio	Texas
United States	Rheumatology Center of San Diego /ID# 170690	San Diego	California
United States	Clinical Investigation Specialists - Skokie /ID# 167468	Skokie	Illinois
United States	Arthritis Northwest, PLLC /ID# 200479	Spokane	Washington
United States	Clinical Research of West Florida, Inc /ID# 169099	Tampa	Florida
United States	ForCare Clinical Research /ID# 206280	Tampa	Florida
United States	DM Clinical Research /ID# 167444	Tomball	Texas
United States	Ocean Rheumatology /ID# 170673	Toms River	New Jersey
United States	North Mississippi Med Clinics /ID# 167377	Tupelo	Mississippi
United States	Iraj Sabahi Research, Inc /ID# 201923	Turlock	California
United States	Inland Rheum Clin Trials Inc. /ID# 167459	Upland	California
United States	STAT Research, Inc. /ID# 200485	Vandalia	Ohio
United States	Deerbrook Medical Associates /ID# 207098	Vernon Hills	Illinois
United States	Arthritis & Osteoporosis Clinic /ID# 167407	Waco	Texas
United States	Medvin Clinical Research /ID# 205731	Whittier	California
United States	PRN of Kansas /ID# 167985	Wichita	Kansas
United States	Advanced Clinical Care /ID# 167367	Worcester	Massachusetts
United States	Clinical Research Ctr Reading /ID# 170708	Wyomissing	Pennsylvania
United States	Florida Medical Clinic /ID# 206279	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Hungary,  Poland,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12	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 (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline indicates improvement in disease activity.	Baseline, Week 12
Secondary	Change From Baseline in Clinical Disease Activity Index (CDAI)	The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician 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, Week 2, Week 4, Week 8, and Week 12
Secondary	Change From Baseline in Simplified Disease Activity Index (SDAI)	The SDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global disease activity assessed by the participant on a visual analogue scale from 0 to 10 (cm), global disease activity assessed by an investigator on a visual analogue scale from 0 to 10 (cm), and serum levels of C-reactive protein (CRP; mg/dL) were included in the SDAI score. Scores on the SDAI range from 0 to 86.with higher scores indicating higher disease activity. A negative change from baseline indicates improvement in disease activity.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12	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 (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6.	At Week 12
Secondary	Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12	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 (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Low Disease Activity (LDA) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than or equal to 3.2.	At Week 12
Secondary	Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria	The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician 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. Low Disease Activity (LDA) based on CDAI is defined as achieving a CDAI of less than or equal to 10.	Week 2, Week 4, Week 8, and Week 12
Secondary	Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria	The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician 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. Complete Remission (CR) based on CDAI is defined as achieving a CDAI of less than or equal to 2.8.	Week 2, Week 4, Week 8, and Week 12
Secondary	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response	Participants who met the following 3 conditions for improvement from baseline were classified as meeting the American College of Rheumatology 20% response (ACR20) 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: Patient's Assessment of Pain (Visual Analog Scale [VAS]); Patient's Global Assessment of Disease Activity (PtGA); Physician's Global Assessment of Disease Activity (PhGA); Health Assessment Questionnaire Disability Index (HAQ-DI); High-sensitivity C-reactive protein (hsCRP)	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response	Participants who met the following 3 conditions for improvement from baseline were classified as meeting the American College of Rheumatology 50% response (ACR50) 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: Patient's Assessment of Pain (Visual Analog Scale [VAS]); Patient's Global Assessment of Disease Activity (PtGA); Physician's Global Assessment of Disease Activity (PhGA); Health Assessment Questionnaire Disability Index (HAQ-DI); High-sensitivity C-reactive protein (hsCRP)	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response	Participants who met the following 3 conditions for improvement from baseline were classified as meeting the American College of Rheumatology 70% response (ACR70) 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: Patient's Assessment of Pain (Visual Analog Scale [VAS]); Patient's Global Assessment of Disease Activity (PtGA); Physician's Global Assessment of Disease Activity (PhGA); Health Assessment Questionnaire Disability Index (HAQ-DI); High-sensitivity C-reactive protein (hsCRP)	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Change From Baseline in Tender Joint Count 68 (TJC68)	Sixty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 68 (worst possible score/68 joints with tenderness). Negative values indicate improvement from baseline.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Change From Baseline in Swollen Joint Count 66 (SJC66)	Sixty-six joints were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 66 (worst possible score/66 joints with swelling). Negative values indicate improvement from baseline.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS])	Participants rated their pain on a visual analogue scale (VAS) of 0 to 100 (mm), with 0 representing no pain and 100 representing the worst possible pain. Negative values indicate improvement from baseline.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Change From Baseline in Patient's Global Assessment of Disease Activity (PGA)	Participants rated their disease activity for the past 24 hours using a Patient's Global Assessment of Disease Activity Global visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA)	The physician assessed a participant's disease activity at the time of the visit using a Physician's Global Assessment of Disease visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)	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. A negative change from baseline in the overall score indicates improvement.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)	C-reactive protein is a blood test marker for inflammation in the body, and levels rise in response to inflammation. A negative change from baseline in indicates improvement.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP])	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 (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline indicates improvement in disease activity.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR)	The DAS28-ESR is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale [VAS] from 0 to 100 mm) are included in the DAS28 -ESR score. Scores on the DAS28-ESR range from 0 to 10; higher scores indicate more disease activity.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Change From Baseline in Morning Stiffness Severity	Morning stiffness severity was assessed by a numeric rating-scale (NRS). Participants rated the severity of morning stiffness during the past week from 0 to 10 with 0 representing "not severe" and 10 "very severe". Negative values indicate improvement from baseline.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)	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. The minimal clinically important difference (MCID) in HAQ-DI is defined as change from Baseline = -0.22 for rheumatoid arthritis.	Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary	Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission	The EULAR Boolean-based definition of remission is as follows: at any time point, a participant must satisfy all of the following: tender joint count =1, swollen joint count =1, C-reactive protein =1 mg/dl and Patient Global Assessment (PGA) =1 (on a 0-10 scale).	Baseline, Week 2, Week 4, Week 8, and Week 12