A Study of Baricitinib (LY3009104) in Participants With Systemic Lupus Erythematosus
- Registration Number
- NCT03616912
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The reason for this study is to see how effective and safe the study drug known as baricitinib is in participants with systemic lupus erythematosus (SLE).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 830
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Have a clinical diagnosis of SLE at least 24 weeks prior to screening.
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Have documentation of having met at least 4 of 11 Revised Criteria for Classification of Systemic Lupus Erythematosus according to the 1997 Update of the 1982 American College of Rheumatology (ACR) criteria for classification of SLE prior to randomization.
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Have a positive antinuclear antibody (ANA) (titer ≥1:80) and/or a positive anti-double-stranded deoxyribonucleic acid (dsDNA), and/or a positive anti-Smith (anti-Sm) as assessed by a central laboratory during screening.
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Have a total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥6 during screening.
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Have a clinical SLEDAI-2K score ≥4 at randomization.
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Have at least 1 British Isles Lupus Assessment Group (BILAG) A score or 2 BILAG B scores during screening.
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Are receiving at least one of the following standard of care medications for SLE:
- A single antimalarial at a stable dose for at least 8 weeks prior to screening
- A single immunosuppressant at a stable dose for at least 8 weeks prior to screening
- An oral corticosteroid, initiated at least 4 weeks prior to screening, at a stable dose ≤40 milligrams/day prednisone (or equivalent) for at least 2 weeks prior to screening. If the participant is not receiving an antimalarial or immunosuppressant, the dose of corticosteroid must be ≥7.5 milligrams/day prednisone (or equivalent)
- Have severe active lupus nephritis.
- Have active central nervous system (CNS) lupus.
- Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data.
- Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection.
- Have received cyclophosphamide (or any other cytotoxic agent) within 12 weeks prior to screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received two placebo tablets: one matching baricitinib 4 milligram (mg) and one matching baricitinib 2 mg administered orally every day (QD) for 52 weeks. Placebo Maximum Extended Enrollment (MEE) Placebo Participants received two placebo tablets: one matching baricitinib 4 mg and one matching baricitinib 2 mg administered orally QD for 52 weeks. 2 mg Baricitinib Placebo Participants received one Baricitinib 2 mg tablet and one placebo tablet matching Baricitinib 4 mg administered QD for 52 weeks. 4 mg Baricitinib (MEE) Placebo Participants received one Baricitinib 4 mg tablet and one placebo tablet matching baricitinib 2 mg administered orally every day (QD) for 52 weeks. 4 mg Baricitinib Placebo Participants received one Baricitinib 4 mg tablet and one placebo tablet matching baricitinib 2 mg administered orally every day (QD) for 52 weeks. 2 mg Baricitinib (MEE) Placebo Participants received one Baricitinib 2 mg tablet and 1 placebo tablet matching Baricitinib 4 mg administered QD for 52 weeks. 2 mg Baricitinib (MEE) Baricitinib Participants received one Baricitinib 2 mg tablet and 1 placebo tablet matching Baricitinib 4 mg administered QD for 52 weeks. 2 mg Baricitinib Baricitinib Participants received one Baricitinib 2 mg tablet and one placebo tablet matching Baricitinib 4 mg administered QD for 52 weeks. 4 mg Baricitinib Baricitinib Participants received one Baricitinib 4 mg tablet and one placebo tablet matching baricitinib 2 mg administered orally every day (QD) for 52 weeks. 4 mg Baricitinib (MEE) Baricitinib Participants received one Baricitinib 4 mg tablet and one placebo tablet matching baricitinib 2 mg administered orally every day (QD) for 52 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response (4 mg Baricitinib) Week 52 SRI-4 response defined as 1)greater than or equal to (\>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score 2)no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and 3)no worsening in Physician Global Assessment (PGA) of Disease Activity (worsening defined as an increase of \>=0.3 from baseline on a 0-3 visual analogue scale).
SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms,or laboratory parameters related to Systemic Lupus Erythematosus (SLE),divided into 9 organ systems. For each organ system A=severe disease,B=moderate disease,C=mild stable disease,D=inactive,but previously active,E=inactive and never affected. PGA assess disease activity on a visual analogue scale from 0 to 3 (1=mild, 2=moderate, 3=severe).
- Secondary Outcome Measures
Name Time Method Time to First Severe Flare Baseline to Week 52 Time to first severe flare was analyzed using a Cox proportional hazards model with treatment group, baseline disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 \[SLEDAI-2K \] \<10; SLEDAI-2K ≥10), baseline corticosteroid dose (\<10 mg/day; ≥10 mg/day prednisone or equivalent), and region fitted as explanatory variables. Participants who did not have severe flare during the flare exposure time period were censored at the end of the flare exposure time.
Change From Baseline in Worst Pain Numeric Rating Scale (NRS) Baseline, Week 52 Participants assessed their worst pain in the last 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The average worst daily pain score was calculated as the mean of the scores over the last 7 days prior to each assessment time point. Higher score indicated severe pain. Least Squares (LS) mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K \<10; \>=10), baseline corticosteroid dose (\<10 mg/day; \>= 10 mg/day prednisone or equivalent), region (North America, Central/South, America/Mexico, Europe, Asia Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.
Percentage of Participants Whose Average Prednisone Dose Had Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52 in Participants Receiving Greater Than 7.5 mg/Day at Baseline Baseline, Week 40 through Week 52 For the analysis of steroid use, steroid dosages were converted to a prednisone equivalent in mg. A responder was defined as having a prednisone reduction by \>=25% from Baseline to \<=7.5 mg/day during Weeks 40 through 52.
Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Total Activity Score ≥10 at Baseline With ≥50% Reduction in CLASI Total Activity Score Week 52 The CLASI is a single-page tool that separately quantifies disease activity and damage. For the activity score, points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. The total score represents the sum of the individual scores and ranges from 0 to 70. Higher scores are awarded for more severe manifestations.
Change From Baseline in Swollen Joint Count Baseline, Week 52 The number of swollen joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as swollen or not swollen. LS mean was calculated using MMRM analysis with treatment, baseline disease activity (total SLEDAI-2K \<10; \>=10), baseline corticosteroid dose (\<10 mg/day; \>=10 mg/day prednisone or equivalent), region (North America, Central/South America/Mexico, Europe, Asia and Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.
Change From Baseline in Tender Joints Count Baseline, Week 52 The number of tender and painful joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as tender or not tender. LS mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K \<10; \>=10), baseline corticosteroid dose (\<10 mg/day; \>=10 mg/day prednisone or equivalent), region (North America, Central/South America/Mexico, Europe, Asia and Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.
Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss) Week 0 (Baseline): 15 minutes (min) and 60 min postdose; Week 4: 2 to 4 hours (hr) postdose; Week 8: 4 to 6 hr postdose; Week 12 and Week 16 predose PK: Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss) was evaluated using population PK approach.
Percentage of Participants Achieving SRI-4 Response - 2 mg Baricitinib Week 52 SRI-4 response defined as 1)greater than or equal to (\>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score 2)no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and 3)no worsening in Physician Global Assessment (PGA) of Disease Activity (worsening defined as an increase of \>=0.3 from baseline on a 0-3 visual analogue scale).
SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms,or laboratory parameters related to Systemic Lupus Erythematosus (SLE),divided into 9 organ systems. For each organ system A=severe disease,B=moderate disease,C=mild stable disease,D=inactive,but previously active,E=inactive and never affected. PGA assess disease activity on a visual analogue scale from 0 to 3 (1=mild, 2=moderate, 3=severe).Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS) Week 52 The LLDAS is a composite measure designed to identify patients achieving a state of low disease activity. The LLDAS response criteria were: (1) SLEDAI-2K \<=4, with no activity in major organ systems (CNS, vascular, renal, cardiorespiratory and constitutional); where "no activity" is defined as all items of SLEDAI-2K within these major organ systems equal to 0. (2) no new features of lupus disease activity compared to previous occurred visit, where the "new feature" is defined as any of the SLEDAI-2K 24 items changed from 0 to greater than 0; (3) PGA (scale 0-3), \<=1; (4) current prednisolone (or equivalent) dose \<=7.5 mg daily.
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Total Score Baseline, Week 52 FACIT-Fatigue score calculated according to a 13-item questionnaire that assess self reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status. Least Squares (LS) mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K \<10; \>=10), baseline corticosteroid dose (\<10 mg/day; \>= 10 mg/day prednisone or equivalent), region (North America, Central/South, America/Mexico, Europe, Asia Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.
Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss) Week 0 (Baseline): 15 minutes (min) and 60 min postdose; Week 4: 2 to 4 hours (hr) postdose; Week 8: 4 to 6 hr postdose; Week 12 and Week 16 predose Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss) was evaluated using population PK approach.
Trial Locations
- Locations (183)
CHU de Liège
🇧🇪Liège, Belgium
University General Hospital of Larissa
🇬🇷Larissa, Greece
Clinical Hospital Dubrava
🇭🇷Zagreb, Croatia
Ryazan State Medical University
🇷🇺Ryazan, Russian Federation
Kuvatov Republican Clinical Hospital
🇷🇺Ufa, Russian Federation
Revmatologie.s.r.o.
🇨🇿Brno, Czechia
Medvin Clinical Research - Weidmann
🇺🇸Whittier, California, United States
Lakes Research, LLC
🇺🇸Miami Lakes, Florida, United States
Joint and Muscle Medical Care
🇺🇸Charlotte, North Carolina, United States
IRIS Research and Development, LLC
🇺🇸Plantation, Florida, United States
Northwell Health
🇺🇸Great Neck, New York, United States
St Luke's Clinic - Intermountain Orthopaedics
🇺🇸Boise, Idaho, United States
SUNY Health Science Center
🇺🇸Brooklyn, New York, United States
St. Joseph Heritage Medical Group
🇺🇸Fullerton, California, United States
MD Medical Corporation
🇺🇸Hemet, California, United States
Office: Hans R Barthel M.D.
🇺🇸Santa Barbara, California, United States
Rheumatology Associates of South Florida
🇺🇸Boca Raton, Florida, United States
West Tennessee Research Institute
🇺🇸Jackson, Tennessee, United States
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Brussel, Belgium
Clinical Research of West Florida, Inc. (Clearwater)
🇺🇸Clearwater, Florida, United States
Metroplex Clinical Research Center
🇺🇸Dallas, Texas, United States
Hospital de Clinicas UNICAMP
🇧🇷Campinas, SP, Brazil
ACRC Studies
🇺🇸Poway, California, United States
Paramount Medical Research
🇺🇸Middleburg Heights, Ohio, United States
LMK Serviços Médicos S/S
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
St. Lawrence Health System
🇺🇸Canton, New York, United States
Hospital de Clinicas de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil
Arthritis and Rheumatic Disease
🇺🇸Aventura, Florida, United States
Buffalo Rheumatology
🇺🇸Orchard Park, New York, United States
Medication Management, LLC
🇺🇸Greensboro, North Carolina, United States
EDUMED - Educação em Saúde Ltda.
🇧🇷Curitiba, Paraná, Brazil
The First Affiliated Hospital of Zhengzhou Universtiy
🇨🇳Zhengzhou, Henan, China
Jiangxi Pingxiang People's Hospital
🇨🇳Pingxiang, Jiangxi, China
The First Affliated Hospital of Soochow University
🇨🇳Suzhou Shi, China
Griffith University
🇦🇺Southport, Australia
Oncovida- Centro de Onco-Hematologia de Mato Grosso
🇧🇷Cuiaba, Brazil
Millennium Research
🇺🇸Ormond Beach, Florida, United States
Glacier View Research Institute - Endocrinology
🇺🇸Kalispell, Montana, United States
Rockford Orthopedic Associates
🇺🇸Rockford, Illinois, United States
East Penn Rheumatology Associates
🇺🇸Bethlehem, Pennsylvania, United States
St. Louis Rheumatology
🇺🇸Saint Louis, Missouri, United States
Santa Casa de Misericordia de Belo Horizonte
🇧🇷Belo Horizonte, MG, Brazil
Ningbo First Hospital
🇨🇳Ningbo, Zhejiang, China
Vseobecna fakultni nemocnice
🇨🇿Praha 2, Czechia
Klinicki Bolnicki Centar Rijeka
🇭🇷Rijeka, Croatia
University Hospital Split
🇭🇷Split, Croatia
ARTHROHELP s.r.o.
🇨🇿Pardubice, Czechia
University General Hospital of Heraklion
🇬🇷Heraklion, Crete, Greece
Euromedica Kyanous Stavros General Hospital
🇬🇷Thessaloniki, Greece
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Chi-Mei Medical Center
🇨🇳Tainan City, Taiwan
Hospital Angeles Lindavista
🇲🇽Mexico city, DF, Mexico
Morales Vargas Centro de Investigacion, S.C.
🇲🇽Leon, Guanajuato, Mexico
Vital Medical Center
🇭🇺Veszprem, Veszprém City, Hungary
Medische Centrum Leeuwarden
🇳🇱Leeuwarden, Fryslân, Netherlands
Universitätsklinikum Würzburg A. ö. R.
🇩🇪Würzburg, Bayern, Germany
Regional Clinical Hospital
🇷🇺Kursk, Russian Federation
Gen Hospital of Athens G Gennimatas
🇬🇷Athens, Attiki, Greece
Meir Medical Center
🇮🇱Kfar Saba, Israel
Clinica de Investigacion en Reumatologia y Obesidad S. C.
🇲🇽Guadalajara, Jalisco, Mexico
Schlosspark Klinik
🇩🇪Berlin, Germany
Chang Gung Memorial Hospital - Kaohsiung Branch
🇨🇳Kaohsiung City, Taiwan
Taipei Medical University Hospital
🇨🇳Taipei, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Accurate Clinical Research
🇺🇸Houston, Texas, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Cincinnati Arthritis Associates
🇺🇸Cincinnati, Ohio, United States
First Affiliated Hospital of the Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
Wuhan Union Hospital
🇨🇳Wuhan, Hubei, China
First affiliated Hospital of Sun Yat-Sen University
🇨🇳Guangzhou, Guangdong, China
China-Japan Union Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China
Shanghai Huashan Hospital Affil to Fu Dan University
🇨🇳Shanghai, China
Zhongshan Hospital, Fudan University
🇨🇳Shanghai, Shanghai, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
China Medical University (CMU) - First Affiliated Hospital
🇨🇳Shenyang, China
People's Hospital of Xinjiang Uygur Autonomous Region
🇨🇳Urumqi, China
Cemdeicy S.C.P.
🇲🇽Merida, Yucatán, Mexico
SER - Serviços Especializados em Reumatologia da Bahia S/S - ME
🇧🇷Salvador, Bahia, Brazil
The Feinstein Institute for Medical Research
🇺🇸Manhasset, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
UPMC Lupus Center of Excellence
🇺🇸Pittsburgh, Pennsylvania, United States
Amarillo Center for Clinical Research
🇺🇸Amarillo, Texas, United States
Accurate Clinical Management
🇺🇸Baytown, Texas, United States
St Vincents Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Spectrum Medical Inc.
🇺🇸Danville, Virginia, United States
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Univ of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Accurate Clinical Research, Inc.
🇺🇸San Antonio, Texas, United States
The Rheumatology Research Unit Sunshine Coast
🇦🇺Maroochydore, Queensland, Australia
Rheumatic Disease Center
🇺🇸Glendale, Wisconsin, United States
Emeritus Research
🇦🇺Camberwell, Victoria, Australia
Medizinische Universität Graz
🇦🇹Graz, Austria
Ordensklinikum Linz GmbH Elisabethinen
🇦🇹Linz, Oberösterreich, Austria
Klinik Hietzing
🇦🇹Wien, Austria
Hospital Alemao Oswaldo Cruz
🇧🇷Sao Paulo, Brazil
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing, Jiangsu, China
Beijing Peking Union Medical College Hospital
🇨🇳Beijing, China
Revmatologicky ustav
🇨🇿Praha 2, Praha, Hlavní Mešto, Czechia
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Universitätsklinikum Freiburg
🇩🇪Freiburg, Baden-Württemberg, Germany
Klinikum der Universität München
🇩🇪München, Bayern, Germany
Universitätsklinikum Köln
🇩🇪Köln, Nordrhein-Westfalen, Germany
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Sachsen, Germany
Charité Universitätsmedizin Berlin Campus Buch
🇩🇪Berlin, Germany
Universität Leipzig - Universitätsklinikum
🇩🇪Leipzig, Sachsen, Germany
Immanuel Krankenhaus Rheuma Klinik Berlin Buch
🇩🇪Berlin, Germany
Hippokration University Hopsital
🇬🇷Thessaloniki, Greece
Bekes Megyei Pandy Kalman Korhaz
🇭🇺Gyula, Bekes, Hungary
Budai Irgalmasrendi Korhaz
🇭🇺Budapest, Hungary
Qualiclinic Kft
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont Reumatologiai Tanszek
🇭🇺Debrecen, Hungary
Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointeze
🇭🇺Budapest, Hungary
Pecsi Tudomanyegyetem Klinikai Kozpont
🇭🇺Pecs, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont I. Belgyogyaszati Klinika
🇭🇺Szeged, Hungary
Carmel Hospital
🇮🇱Haifa, Ḥeifā, Israel
CIMAB SA de CV
🇲🇽Torreon, Coahuila, Mexico
Cliditer Sa de CV
🇲🇽Mexico City, Distrito Federal, Mexico
Centro Integral en Reumatologia SA de CV
🇲🇽Guadalajara, Jalisco, Mexico
Centro de Estudios de Investigacion Metabolicos y Cardiovasculares
🇲🇽Guadalajara, Jalisco, Mexico
Köhler & Milstein Research
🇲🇽Merida, Yucatan, Mexico
Centro Peninsular de Investigacion S.C.P
🇲🇽Merida, Yucatán, Mexico
Clinosar Mexico S.A. de C.V
🇲🇽Mexico City, Mexico
City Hospital # 7
🇷🇺Kazan, Russian Federation
City Clinical Hospital 1 named after N.I. Pirogov
🇷🇺Moscow, Russian Federation
Reafan
🇷🇺Novosibirsk, Russian Federation
Rheumatology Institute RAMS
🇷🇺Moscow, Russian Federation
Healthy Family
🇷🇺Novosibirsk, Russian Federation
Institute of Cytology and Genetics of Siberian Branch of Russian Academy of Medical Sciences
🇷🇺Novosibirsk, Russian Federation
Orenburg State Medical Academy of Roszdrav
🇷🇺Orenburg, Russian Federation
Regional Hospital - Omsk
🇷🇺Omsk, Russian Federation
Departmental Hospital at Smolensk Station "rzhd" JSC
🇷🇺Smolensk, Russian Federation
Chang Gung Memorial Hospital - Linkou
🇨🇳Kuei Shan Hsiang, Taoyuan Hsien, Taiwan
Hualien Tzu-Chi Hospital
🇨🇳Dalin Township, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Maidstone Hospital
🇬🇧Maidstone, Kent, United Kingdom
Whipps Cross University Hospital
🇬🇧London, Surrey, United Kingdom
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Arthritis & Rheumatology Center of Oklahoma PLLC
🇺🇸Oklahoma City, Oklahoma, United States
Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust
🇬🇧Doncaster, United Kingdom
St. George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Achieve Clinical Research, LLC
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Denver Arthritis Clinic - Lowry
🇺🇸Denver, Colorado, United States
ForCare Clinical Research
🇺🇸Tampa, Florida, United States
Universitätsklinikum Tübingen
🇩🇪Tubingen, Baden-Wurttemberg, Germany
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz
🇩🇪Mainz, Rheinland-Pfalz, Germany
Piedmont Healthcare
🇺🇸Atlanta, Georgia, United States
Arthritis and Rheumatology Center of South Florida
🇺🇸Margate, Florida, United States
Atlanta Center for Clinical Research
🇺🇸Atlanta, Georgia, United States
Albuquerque Center for Rheumatology
🇺🇸Albuquerque, New Mexico, United States
PMG Research of Wilmington
🇺🇸Wilmington, North Carolina, United States
Dr. Dhiman Basu Private Practice
🇺🇸Colleyville, Texas, United States
Rheumatology Center of Houston
🇺🇸Houston, Texas, United States
Arthritis Clinic Of Central Texas
🇺🇸San Marcos, Texas, United States
Southwest Rheumatology, P.A.
🇺🇸Mesquite, Texas, United States
Centro de Estudos em Terapias Inovadoras-CETI
🇧🇷Curitiba, Paraná, Brazil
Russian State Medical University
🇷🇺Moscow, Russian Federation
Precision Comprehensive Clinical Research Solutions
🇺🇸Fort Worth, Texas, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Clinical Research Institute of Michigan, LLC
🇺🇸Saint Clair Shores, Michigan, United States
UZ Leuven
🇧🇪Leuven, Vlaams Brabant, Belgium
CIP-Centro Internacional de Pesquisa
🇧🇷Goiania, Goiás, Brazil
Arizona Arthritis & Rheumatology Research, PLLC
🇺🇸Glendale, Arizona, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
New England Research Associates
🇺🇸Bridgeport, Connecticut, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Allied Clinical Research
🇺🇸Reno, Nevada, United States
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Vita Verum Egeszsegugyi Szolgaltato Bt
🇭🇺Székesfehérvár, Hungary
Centro de Investigación y Tratamiento Reumatológico S.C
🇲🇽Ciudad De México, Mexico
Centro de Alta Especialidad Reumatologia e Inv Potosi, S.C.
🇲🇽San Luis Potosi, Mexico
Vrije Universiteit Medisch Centrum Amsterdam
🇳🇱Amsterdam, Netherlands
LLC MK Med
🇷🇺St. Petersburg, Saint Petersburg, Russian Federation
Chelyabinsk Regional Clinical Hospital
🇷🇺Chelyabinsk, Russian Federation
Russian Medical Military Academy n.a. S.M. Kirov
🇷🇺Saint Petersburg, Russian Federation
Universitätsspital Basel
🇨🇭Basel, Basel Stadt, Switzerland
Cantonal Hospital St.Gallen
🇨🇭st.Gallen, Sankt Gallen, Switzerland
Kaohsiung Veterans General Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Investigación Biomédica para el Desarrollo de Fármacos S.A. de C.V.
🇲🇽Zapopan, Jalisco, Mexico
Guy's Hospital
🇬🇧London, United Kingdom
Peking University First Hospital
🇨🇳Beijing, China