Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)
- Conditions
- Systemic Lupus Erythematosus (SLE)
- Interventions
- Drug: Placebo for Rozibafusp Alfa
- Registration Number
- NCT04058028
- Lead Sponsor
- Amgen
- Brief Summary
The purpose of this study is to determine if Rozibafusp Alfa could be a useful therapeutic agent in the current treatment landscape where subjects with SLE have ongoing disease activity despite treatment with standard of care therapies.
- Detailed Description
This is a Bayesian adaptive phase 2b, multi-center, double-blind, randomized, placebo-controlled, 52-week, dose-ranging study in subjects with active SLE and inadequate response to SOC therapies including oral corticosteroids (OCS), immunosuppressants and immunomodulators. Previous biologic use is allowed with an adequate washout period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 244
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo for Rozibafusp Alfa Placebo for Rozibafusp Alfa Placebo Investigational product solution in vial Rozibafusp Alfa, Dose A Rozibafusp Alfa Investigational product solution in vial Rozibafusp Alfa, Dose C Rozibafusp Alfa Investigational product solution in vial Rozibafusp Alfa, Dose B Rozibafusp Alfa Investigational product solution in vial
- Primary Outcome Measures
Name Time Method Number of Participants With a SLE Responder Index (SRI-4) Response at Week 52 Week 52 SRI-4 response at Week 52 is defined as a ≥ 4-point decrease in the hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score, and no new British Isles Lupus Assessment Group (BILAG) 2004 A score, no greater than 1 new BILAG B domain scores compared with baseline, and a less than 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3), and no use of more than protocol allowed therapies.
- Secondary Outcome Measures
Name Time Method Number of Participants With a SRI-4 Response at Week 24 Week 24 SRI-4 response at Week 24 is defined as a ≥ 4-point decrease in the hSLEDAI score, and no new BILAG 2004 A score, no greater than 1 new BILAG B domain scores compared with baseline, and a less than 0.3-point deterioration from baseline in PGA (scale 0 to 3), and no use of more than protocol allowed therapies.
Number of Participants Who Achieved a BILAG Based Combined Lupus Assessment (BICLA) Response at Week 24 Week 24 The BICLA response is defined as:
1. An improvement in baseline BILAG domain scores across all body systems with moderate (domain B) or severe disease activity (domain A)
2. No new BILAG 2004 A domain score and no \> 1 new BILAG 2004 B domain scores compared with baseline
3. No worsening of the hSLEDAI score from baseline
4. No ≥ 0.3-point deterioration from baseline in PGA
5. No use of more than protocol-allowed therapies
6. No disallowed changes in concomitant medications, mainly including increases in corticosteroids, immunosuppressants.Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) Response at Week 52 Week 52 LLDAS was defined as meeting all the following conditions:
1. hSLEDAI ≤ 4, with no activity in major organ system (renal, central nervous system \[CNS\], cardiopulmonary, vasculitis, fever) and hemolytic anemia or gastrointestinal activity
2. No new lupus disease activity as compared with the previous assessment
3. PGA ≤ 1 (on a scale of 0 to 3)
4. Current prednisone or equivalent dose of ≤ 7.5 mg/day
5. Well-tolerated standard maintenance doses of immunosuppressive drugs and approved treatments, as allowed and specified in the protocol.Number of Participants Who Achieved a BICLA Response at Week 52 Week 52 The BICLA response is defined as:
1. An improvement in baseline BILAG domain scores across all body systems with moderate (domain B) or severe disease activity (domain A)
2. No new BILAG 2004 A domain score and no \> 1 new BILAG 2004 B domain scores compared with baseline
3. No worsening of the hSLEDAI score from baseline
4. No ≥ 0.3-point deterioration from baseline in PGA
5. No use of more than protocol-allowed therapies
6. No disallowed changes in concomitant medications, mainly including increases in corticosteroids, immunosuppressants.Number of Participants Achieving a SRI-4 Response With a Reduction of Oral Corticosteroids (OCS) to ≤ 7.5 mg/Day by Week 44 and Sustained Through Week 52 In Participants With a Baseline OCS Dose ≥ 10 mg/Day Up to Week 52 SRI-4 response is defined as a ≥ 4-point decrease in the hSLEDAI score, and no new BILAG 2004 A score, no greater than 1 new BILAG B domain scores compared with baseline, and a less than 0.3-point deterioration from baseline in PGA (scale 0 to 3), and no use of more than protocol allowed therapies. Participants also had to meet a reduction if OCS to ≤ 7.5 mg/day by Week 44 sustained through Week 52.
Annualized Moderate and Severe Flare Rate Over 52 Weeks as Measured by Safety of Estrogens in Systemic Lupus Erythematosus National Assessment [SELENA] -Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] Flare Index (SFI) Up to Week 52 The SFI, serves as a composite outcome measure incorporating the SELENA-SLEDAI score, and classifications of flares into mild, moderate, and severe, along with the PGA of disease activity. The SFI details specific clinical manifestations for each organ system and categorizes flares into mild, moderate, and severe based on treatment decisions. Moderate and severe flare: • Moderate: meeting criteria like SELENA-SLEDAI score change of 3 to 12 points, SLE symptom development, prednisone dose increase, non-steroidal anti-inflammatory drugs (NSAIDs)/hydrochloroquine addition, or PGA score increase by 1 to 2.5. • Severe: meeting criteria like SELENA-SLEDAI increase over 12 points, onset or worsening of severe symptoms, significant prednisone dose escalation, introduction of potent immunosuppressants, hospitalization, or PGA score reaching 2.5 or higher. Annualized flare rate was calculated as the number of flares divided by flare exposure time in days, multiplied by 365.25 for each Group.
Annualized Severe Flare Rate Over 52 Weeks as Measured by SFI Up to Week 52 The SFI, serves as a composite outcome measure incorporating the SELENA-SLEDAI score, and classifications of flares into mild, moderate, and severe, along with the PGA of disease activity. The SFI details specific clinical manifestations for each organ system and categorizes flares into mild, moderate, and severe based on treatment decisions. Severe flare: meeting criteria like SELENA-SLEDAI increase over 12 points, onset or worsening of severe symptoms, significant prednisone dose escalation, introduction of potent immunosuppressants, hospitalization, or PGA score reaching 2.5 or higher. The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days, multiplied by 365.25 for each Group.
Annualized Flares Rate Over 52 Weeks as Measured by BILAG Score Designation of "Worse" or "New" Resulting in a B-Score In ≥ 2 Organs or an A-Score in ≥ 1 Organ Up to Week 52 The BILAG flare index was derived from BILAG 2004, as measured by BILAG score designation of 'worse' or 'new' resulting in a B score in \>= 2 organs or an A score in \>= 1 organ.
The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days, multiplied by 365.25 for each Group.Number of Participants With ≥6 Tender and Swollen Joints in Hands and Wrists at Baseline Achieving ≥50% Improvement From Baseline at Weeks 12, 24, 36, and 52 Week 12, 24, 36, and 52 The tender and swollen joint count is a physical assessment where for each swollen and tender joint a score of 1 is assigned. Scores are then summed up to provide a total score for both swollen and tender joints. Higher total score indicate a severe disease activity and a lower score indicates a lees severe disease activity.
Number of Participants With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Activity Score ≥8 at Baseline Achieving ≥50% Improvement From Baseline at Weeks 12, 24, 36, and 52 Week 12, 24, 36, and 52 The CLASI is an assessment tool consisting of two scores: one for disease activity and one for damage. Activity Score: Ranges from 0 to 70, and is assessed based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss, and non-scarring alopecia. Higher scores indicate more severe disease activity.
Damage Score: Ranges from 0 to 56, and is evaluated through dyspigmentation and scarring, including scarring alopecia. Dyspigmentation that remains visible for more than 12 months is considered permanent, and its score is doubled. Higher scores indicate greater damage.Change From Baseline in Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a Instrument (PROMIS-Fatigue SF7a) Score at Weeks 12, 24, 36, 44, and 52 Week 12, 24, 36, 44, and 52 The PROMIS-Fatigue SF7a is a 7-item instrument that assesses the experience of fatigue as well as its impact on physical, mental and social activities. Each item is scored on a 5-point Likert scale, ranging from "1" (Never) to "5" (Always). The scores of all 7 items are summed up with a total raw score range of 7(low level of fatigue)-35(high level of fatigue). Raw scores are converted to a T-score ranging from 29.4(low level of fatigue)-83.2(high level of fatigue).
Change From Baseline in the Short Form 36 Version 2 (SF-36v2) Health Survey Physical Component Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Mental Component Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Physical Functioning Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Physical Role Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Bodily Pain Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey General Health Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Vitality Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Social Role Functioning Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Emotional Role Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in the SF-36v2 Health Survey Mental Health Domain Score at Weeks 12, 24, 36, 44 and 52 Week 12, 24, 36, 44, and 52 The SF-36v2 (acute version) Health Survey consists of 36 items and serves as a patient-reported measure of health status. It assesses 8 domains of health-related quality of life: physical limitations, social limitations, role limitations due to physical health, bodily pain, mental health, role limitations due to emotional health, vitality, and general health perceptions. Each domain of the SF-36v2 produces a score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Change From Baseline in Lupus Quality of Life Questionnaire (LupusQoL) Score at Weeks 12, 24, 36, 44, and 52 Week 12, 24, 36, 44, and 52 The LupusQoL questionnaire consists of 8 domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue. Each item in the questionnaire is scored on a 5 point scale and items within a given domain are summed and converted to a 0-100 scale. Each domain is scored 0-100 with higher scores representing better quality of life in the specific domain. Lower scores signify poorer quality of life within the domain.
Change From Baseline in Patient Global Assessment Score (PtGA) at Weeks 12, 24, 36, 44, and 52 Week 12, 24, 36, 44, and 52 The PtGA assesses disease activity on a 10 cm numeric rating scale (NRS; 0 to 10 cm). The scale for the assessment ranges from "very well" (0) to "very poor" (10).
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) Up to approximately 68 weeks An adverse event (AE) was any negative medical occurrence linked to an intervention in humans, regardless of its relation to the intervention. Treatment-emergent AEs (TEAEs) were those that occurred after the first intervention dose. A serious adverse event (SAE) included outcomes such as death, life-threatening situations, hospitalization or an extended hospital stay, significant incapacity, congenital defects, or other crucial medical events. AE severity followed the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 scale: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death). Clinically significant laboratory results or other assessments (e.g., ECGs, scans, vital signs) that worsened from baseline and were deemed important by the investigator, independent of disease progression, were also considered.
Serum Concentration of Rozibafusp Alfa Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 36, Week 44, Week 52, Week 56, Week 60, Week 64, and Week 68 Terminal Half-life of Rozibafusp Alfa Up to Week 68
Trial Locations
- Locations (142)
University of California Los Angeles
🇺🇸Los Angeles, California, United States
The Emory Clinic
🇺🇸Atlanta, Georgia, United States
Rheumatic Disease Clinical Research Center LLC
🇺🇸Houston, Texas, United States
TriWest Research Associates
🇺🇸San Diego, California, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Centro Peninsular de Investigación Clínica
🇲🇽Merida, Yucatán, Mexico
Shared Health Inc. operating the Health Sciences Centre Winnipeg
🇨🇦Winnipeg, Manitoba, Canada
Morales Vargas Centro de Investigacion SC
🇲🇽Leon, Guanajuato, Mexico
University of Florida
🇺🇸Gainesville, Florida, United States
Instituto de Investigaciones Clinicas Quilmes
🇦🇷Quilmes, Buenos Aires, Argentina
Instituto Medico de Alta Complejidad San Isidro
🇦🇷San Isidro, Buenos Aires, Argentina
Centre Hospitalier Universitaire de Toulouse - Hopital Purpan
🇫🇷Toulouse, France
Centro Medico Privado de Reumatologia
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
Attiko Hospital
🇬🇷Athens, Greece
Gifu University Hospital
🇯🇵Gifu-shi, Gifu, Japan
Sasebo Chuo Hospital
🇯🇵Sasebo-shi, Nagasaki, Japan
University of Maryland School of Medicine Division of Rheumatology
🇺🇸Baltimore, Maryland, United States
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
National Hospital Organization Tokyo Medical Center
🇯🇵Meguro-ku, Tokyo, Japan
Centre Hospitalier Universitaire Dijon Bourgogne - Hopital Francois Mitterrand
🇫🇷Dijon Cedex, France
Centre Hospitalier Universitaire de Strasbourg - Nouvel hopital civil
🇫🇷Strasbourg, France
University of California San Diego
🇺🇸La Jolla, California, United States
Lakes Research LLC
🇺🇸Miami Lakes, Florida, United States
Imaging Endpoints
🇺🇸Scottsdale, Arizona, United States
Fundacion Respirar - Centro Medico Dra De Salvo
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Articularis Healthcare Group Inc dba Low Country Rheumatology
🇺🇸Summerville, South Carolina, United States
Clinical Mayo - Clinica Mayo de Urgencias Medicas Cruz Blanca S.R.L
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
University Multiprofile Hospital for Active Treatment - Kaspela EOOD
🇧🇬Plovdiv, Bulgaria
Medical Centre Synexus Sofia EOOD - Branch Stara Zagora
🇧🇬Stara Zagora, Bulgaria
University Hospital of Heraklion
🇬🇷Heraklion, Greece
Kobe University Hospital
🇯🇵Kobe-shi, Hyogo, Japan
Hopital Pitie-Salpetriere
🇫🇷Paris, France
Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin
🇫🇷Bordeaux, France
Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez
🇫🇷Lille cedex 01, France
Universitätsklinikum Leipzig AöR
🇩🇪Leipzig, Germany
Vita Verum Medical Bt
🇭🇺Szekesfehervar, Hungary
Azienda Ospedaliera Universitaria Pisana
🇮🇹Pisa, Italy
Okayama University Hospital
🇯🇵Okayama-shi, Okayama, Japan
Juntendo University Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
St Lukes International Hospital
🇯🇵Chuo-ku, Tokyo, Japan
General University Hospital of Patras Panagia i Voithia
🇬🇷Patra, Greece
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Juntendo University Urayasu Hospital
🇯🇵Urayasu-shi, Chiba, Japan
Centro de Investigacion en Artritis y Osteoporosis SC
🇲🇽Mexicalli, Baja California Norte, Mexico
1 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej
🇵🇱Lublin, Poland
Clinical Best Solutions Spolka z ograniczona odpowiedzialnoscia Spolka komandytowa
🇵🇱Lublin, Poland
Seirei Hamamatsu General Hospital
🇯🇵Hamamatsu-shi, Shizuoka, Japan
Centro Integral en Reumatologia SA de CV
🇲🇽Guadalajara, Jalisco, Mexico
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
LLC Medical Sanitary Unit №157
🇷🇺Saint Petersburg, Russian Federation
Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Korea, Republic of
Keio University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Centro Medico del Angel SC
🇲🇽Mexicali, Baja California Norte, Mexico
Tomed Tomasz Miszalski-Jamka Centrum Medyczne
🇵🇱Krakow, Poland
Synexus Polska Spolka z ograniczona odpowiedzialnoscia
🇵🇱Warszawa, Poland
LLC Center of medicine Healthy family
🇷🇺Novosibirsk, Russian Federation
LLC Center of general medicine
🇷🇺Novosibirsk, Russian Federation
FSBSI SRI of Rheumatology na V A Nasonova
🇷🇺Moscow, Russian Federation
Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz
🇵🇹Lisboa, Portugal
Centro Hospitalar Universitario de Lisboa Norte, EPE - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Centro Hospitalar do Porto EPE - Hospital de Santo Antonio
🇵🇹Porto, Portugal
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Southwest Florida Clinical Research Center
🇺🇸Tampa, Florida, United States
Arthritis and Rheumatology Center of Oklahoma PLLC
🇺🇸Oklahoma City, Oklahoma, United States
AdventHealth Medical Group
🇺🇸Tampa, Florida, United States
Medvin Clinical Research
🇺🇸Covina, California, United States
Southern California Permanente Medical Group
🇺🇸Fontana, California, United States
Stanford University Hospitals and Clinics
🇺🇸Palo Alto, California, United States
Centre for Rheumatology Immunology and Arthritis
🇺🇸Fort Lauderdale, Florida, United States
Piedmont Atlanta Hospital
🇺🇸Atlanta, Georgia, United States
Clinic of Robert Hozman, MD - Clinical Investigational Specialists, Inc
🇺🇸Skokie, Illinois, United States
New York University Langone Orthopedic Center
🇺🇸New York, New York, United States
Feinstein Institute for Medical Research
🇺🇸Manhasset, New York, United States
Hospital For Special Surgery
🇺🇸New York, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Joint and Muscle Research Institute
🇺🇸Charlotte, North Carolina, United States
DJL Clinical Research PLLC
🇺🇸Charlotte, North Carolina, United States
The Oklahoma Center for Arthritis Therapy and Research Inc
🇺🇸Tulsa, Oklahoma, United States
Penn State Milton South Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Trinity Universal Research Associates, Inc
🇺🇸Carrollton, Texas, United States
Southwest Rheumatology
🇺🇸Mesquite, Texas, United States
Dom Centro de Reumatologia
🇦🇷Caba, Buenos Aires, Argentina
Hospital Militar Central - Cirujano Mayor Dr Cosme Argerich
🇦🇷Buenos Aires, Distrito Federal, Argentina
CER San Juan - Centro Polivalente de Asistencia e Investigacion Clinica
🇦🇷San Juan, Argentina
Multiprofile Hospital for Active Treatment Trimontium OOD
🇧🇬Plovdiv, Bulgaria
Holdsworth House Medical Practice
🇦🇺Sydney, New South Wales, Australia
University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
🇧🇬Plovdiv, Bulgaria
Medical Center Excelsior OOD
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
🇧🇬Sofia, Bulgaria
Medical Center Academy EOOD
🇧🇬Sofia, Bulgaria
Medical Centre Synexus Sofia EOOD
🇧🇬Sofia, Bulgaria
University of Calgary Cumming School of Medicine
🇨🇦Calgary, Alberta, Canada
Groupe de recherche en maladies osseuses Incorporated
🇨🇦Quebec, Canada
Synexus Czech sro
🇨🇿Praha 2, Czechia
Revmatologicky ustav
🇨🇿Praha 2, Czechia
CHU Hôpital Côte de Nacre
🇫🇷Caen Cedex 9, France
Centre Hospitalier Universitaire de Reims - Hopital Robert Debre
🇫🇷Reims Cedex, France
Centre Hospitalier Universitaire de Toulouse - Hopital Rangueil
🇫🇷Toulouse Cedex 9, France
Johannes Gutenberg Universitaet Mainz
🇩🇪Bad Kreuznach, Germany
Laiko General Hospital
🇬🇷Athens, Greece
Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz
🇭🇺Gyula, Hungary
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
National Hospital Organization Chibahigashi National Hospital
🇯🇵Chiba-shi, Chiba, Japan
IRCCS Istituto Clinico Humanitas
🇮🇹Rozzano MI, Italy
Hospital of the University of Occupational and Environmental Health Japan
🇯🇵Kitakyushu-shi, Fukuoka, Japan
Sapporo City General Hospital
🇯🇵Sapporo-shi, Hokkaido, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Kanazawa University Hospital
🇯🇵Kanazawa-shi, Ishikawa, Japan
National University Corporation Tohoku University Tohoku University Hospital
🇯🇵Sendai-shi, Miyagi, Japan
Shinshu University Hospital
🇯🇵Matsumoto-shi, Nagano, Japan
Nagasaki University Hospital
🇯🇵Nagasaki-shi, Nagasaki, Japan
National Hospital Organization Nagasaki Medical Center
🇯🇵Omura-shi, Nagasaki, Japan
Kurashiki Medical Clinic
🇯🇵Kurashiki-shi, Okayama, Japan
The University of Tokyo Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Ajou University Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Centro Mexicano de Desarrollo de Estudios Clinicos
🇲🇽Ciudad de Mexico, Mexico
Synexus Polska Spzoo
🇵🇱Wroclaw, Poland
Hospital Garcia de Orta, EPE
🇵🇹Almada, Portugal
Somed cr
🇵🇱Lodz, Poland
Silmedic Spzoo
🇵🇱Katowice, Poland
SOMED CR
🇵🇱Warszawa, Poland
Sanus Szpital Specjalistyczny Spzoo
🇵🇱Stalowa Wola, Poland
Futuremeds spolka z ograniczona odpowiedzialnoscia
🇵🇱Wroclaw, Poland
Centro Hospitalar Universtario de Sao Joao, EPE
🇵🇹Porto, Portugal
Limited liability company Scientific Research Medical Complex Your Health
🇷🇺Kazan, Russian Federation
State Budget Medical Institution Sverdlovsk Regional Clinical Hospital N1
🇷🇺Ekaterinburg, Russian Federation
LLC Medical center Revma Med
🇷🇺Kemerovo, Russian Federation
LLC Medical Center Maksimum Zdorovia
🇷🇺Kemerovo, Russian Federation
Hospital Universitari Vall d Hebron
🇪🇸Barcelona, Cataluña, Spain
Hospital Infanta Luisa
🇪🇸Sevilla, Andalucía, Spain
Complexo Hospitalario Universitario A Coruña
🇪🇸A Coruña, Galicia, Spain
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Heuer Medical Doctor Research LLC
🇺🇸Orlando, Florida, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Austin Regional Clinic Specialty Research
🇺🇸Austin, Texas, United States
Tuen Mun Hospital
🇭🇰New Territories, Hong Kong