A Study of Guselkumab in Participants With Active Lupus Nephritis
- Conditions
- Lupus Nephritis
- Interventions
- Registration Number
- NCT04376827
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy of guselkumab in participants with active lupus nephritis (LN).
- Detailed Description
Guselkumab is a monoclonal antibody (mAb) that binds to human interleukin (IL)-23 with high affinity and blocks binding of extracellular IL-23 to cell surface IL-23 receptor, inhibiting IL 23 specific intracellular signaling and subsequent activation and cytokine production. It is used in treatment of plaque psoriasis, psoriatic arthritis, generalized pustular psoriasis, erythrodermic psoriasis. Lupus is a heterogeneous autoimmune disease with lesions confined to skin (cutaneous lupus erythematosus \[CLE\]) to others that involve 1 or more vital internal organs (systemic lupus erythematosus \[SLE\]). Renal involvement due to SLE is termed lupus nephritis (LN). There is a high unmet need for new treatment options in LN that are safe and effective, especially new therapies that can provide improved long-term efficacy over currently available therapies. This study will evaluate safety and efficacy of guselkumab added to standard-of-care compared to placebo added to standard-of-care. Total duration of study is up to 68 weeks: a less than or equal to 8 week screening period, a 48 week double-blind treatment period, a 12 week safety follow-up period after last dose. Participants who complete the assessments at Week 52 and have achieved complete renal response (CRR) may have the option to participate in the long-term extension (LTE) of study through Week 152 and the 12-week safety follow-up visit. Hypothesis of this study is that guselkumab plus standard-of-care is superior to placebo plus standard-of-care in participants with active LN as measured by the proportion of participants inducing at least a 50 percentage reduction of proteinuria with protocol specified steroid tapering regimen at Week 24. Safety assessments include Adverse events (AEs), clinical laboratory tests (hematology and chemistry), systolic and diastolic blood pressures over time, monitoring for hypersensitivity reactions, AEs temporally associated with infusion, injection-site reactions, suicidality assessment, and early detection of active tuberculosis (TB).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 33
- At screening and randomization, must be receiving oral glucocorticoids at minimum prednisone equivalent dose of 10 milligrams per day (mg/day) and maximum 1 mg/kg/day or less than or equal to (<=) 60 mg/day, whichever is lower. Treated for greater than or equal to (>=) 6 weeks with stable dosing >=2 weeks before randomization
- If receiving angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blockers (ARB), a stable dose for at least 2 weeks prior to randomization
- Positive antinuclear antibody (ANA; >= 1:80 titer by central laboratory test) or anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies (>=30 international units per milliliter ([U/mL] by central laboratory test) detected at screening
- Kidney biopsy documentation of active International Society of Nephrology (ISN)/Renal Pathology Society (RPS) proliferative nephritis: Class III-IV (with or without class V membranous nephritis) within the last 6 months prior to screening or performed during screening
- Urine Protein to Creatinine Ratio (UPCR) >= 1.0 milligram/milligram (mg/mg) assessed on 2 first morning urine void specimens during screening. These 2 specimens do not need to be on consecutive days, however, 2 samples must be tested with UPCR >= 1.0 mg/mg in a row. The UPCR requirement must be met after at least 8 weeks of mycophenolate mofetil (MMF)/mycophenolic acid (MPA) treatment, and after stable glucocorticoid dosing is achieved at the dose intended at time of randomization
- Comorbidities (other than lupus nephritis [LN], example, asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic glucocorticoids within the previous 12 months
- Has other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), psoriatic arthritis (PsA), RA/lupus overlap, psoriasis, Crohn's disease, or active Lyme disease
- Received PO (orally) or intravenously (IV) cyclophosphamide within 3 months prior to randomization
- History of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, before screening
- History of being human immunodeficiency virus (HIV) antibody-positive, or tests positive for HIV at screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Guselkumab+Standard of Care Guselkumab Dose 1 Participants will receive guselkumab Dose 1 intravenously (IV) at Weeks 0, 4 and 8 and guselkumab Dose 2 subcutaneous (SC) every 4 weeks (q4w) from Week 12 through Week 48 along with standard-of-care treatment of mycophenolate mofetil (MMF)/mycophenolic acid (MPA) and glucocorticoids. Participants who achieved complete renal response (CRR) at Week 48 and 52 and have completed the Week 52 assessment may have the option to participate in the long-term extension (LTE). Guselkumab+Standard of Care Guselkumab Dose 2 Participants will receive guselkumab Dose 1 intravenously (IV) at Weeks 0, 4 and 8 and guselkumab Dose 2 subcutaneous (SC) every 4 weeks (q4w) from Week 12 through Week 48 along with standard-of-care treatment of mycophenolate mofetil (MMF)/mycophenolic acid (MPA) and glucocorticoids. Participants who achieved complete renal response (CRR) at Week 48 and 52 and have completed the Week 52 assessment may have the option to participate in the long-term extension (LTE). Guselkumab+Standard of Care Standard-of-care treatment Participants will receive guselkumab Dose 1 intravenously (IV) at Weeks 0, 4 and 8 and guselkumab Dose 2 subcutaneous (SC) every 4 weeks (q4w) from Week 12 through Week 48 along with standard-of-care treatment of mycophenolate mofetil (MMF)/mycophenolic acid (MPA) and glucocorticoids. Participants who achieved complete renal response (CRR) at Week 48 and 52 and have completed the Week 52 assessment may have the option to participate in the long-term extension (LTE). Placebo+Standard of Care Placebo Participants will receive placebo IV at Weeks 0, 4 and 8 and placebo SC q4w from Week 12 through Week 48 along with standard-of-care treatment of MMF/MPA and glucocorticoids. Participants who achieved complete renal response (CRR) at Week 48 and 52 and have completed the Week 52 assessment may have the option to participate in the LTE of the study. Placebo+Standard of Care Standard-of-care treatment Participants will receive placebo IV at Weeks 0, 4 and 8 and placebo SC q4w from Week 12 through Week 48 along with standard-of-care treatment of MMF/MPA and glucocorticoids. Participants who achieved complete renal response (CRR) at Week 48 and 52 and have completed the Week 52 assessment may have the option to participate in the LTE of the study.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving at Least 50 Percent (%) Decrease From Baseline in Proteinuria at Week 24 Week 24 Percentage of participants achieving at least 50% decrease in proteinuria from baseline at Week 24 was reported. Proteinuria analysis was based on urine protein creatinine ratio (UPCR) and was defined as the presence of an excess of serum proteins in the urine, which may be an early sign of kidney disease.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Achieved Complete Renal Response (CRR) at Week 24 Week 24 Percentage of participants who achieved CRR at Week 24 were reported. CRR was defined as UPCR less than (\<) 0.5 milligrams per milligrams (mg/mg), estimated glomerular filtration rate (eGFR) greater than or equal to (\>=) 60 milliliter per minute per 1.73 meter square (mL/min/1.73m\^2) or no confirmed decrease \>=20% from baseline and prednisone dose less than or equal to (\<=) 10 milligrams per day (mg/d). Participant was considered as achieved CRR who did not discontinue study intervention for any reason excluding COVID-19 related discontinuations or met the medication intercurrent event (exceeded baseline glucocorticoid dose, increase above 10 mg/d prednisone equivalent after Week 12, use of new or increased dose of concomitant medication related to LN or other immunosuppressive agents, within 8 weeks prior to the outcome measure (OM) time point (Week 24) or initiation of prohibited medications at any time prior to the endpoint time point (Week 24).
Percentage of Participants Who Achieved CRR at Week 52 Week 52 Percentage of participants who achieved CRR at Week 52 were reported. CRR was defined as UPCR less than (\<) 0.5 mg/mg, eGFR \>= 60 mL/min/1.73m\^2 or no confirmed decrease \>=20% from baseline and prednisone dose \<= 10 mg/d. Participant was considered as achieved CRR who did not discontinue study intervention for any reason excluding COVID-19 related discontinuations or met the medication intercurrent event (exceeded baseline glucocorticoid dose, increase above 10 mg/d prednisone equivalent after Week 12, use of new or increased dose of concomitant medication related to LN or other immunosuppressive agents, within 8 weeks prior to the outcome measure time point (Week 52) or initiation of prohibited medications at any time prior to the outcome measure time point (Week 52).
Percentage of Participants Achieving a Sustained Reduction in Steroid Dose <=10 mg/d of Prednisone or Equivalent From Week 16 Through Week 24 From Week 16 through Week 24 Percentage of participants achieving a sustained reduction in steroid dose less than or equal to (\<=) 10 mg/day of prednisone or equivalent from week 16 through Week 24were reported.
Percentage of Participants Achieving at Least 50% Decrease in Proteinuria From Baseline at Week 52 Week 52 Percentage of participants achieving at least 50% decrease in proteinuria from baseline at Week 52 were reported. Proteinuria analysis was based on urine protein creatinine ratio (UPCR) and was defined as the presence of an excess of serum proteins in the urine, which may be an early sign of kidney disease.
Percentage of Participants With Urine Protein to Creatinine Ratio (UPCR) < 0.5 mg/mg at Week 24 Week 24 Percentage of participants with UPCR \<0.5 mg/mg at Week 24 were reported.
Percentage of Participants With UPCR < 0.75 mg/mg at Week 24 Week 24 Percentage of participants with UPCR less than 0.75 mg/mg at Week 24 were reported.
Percentage of Participants Who Achieved CRR Through Week 24 Up to Week 24 Percentage of participants who achieved CRR through Week 24 was reported. CRR was defined as UPCR\<0.5 mg/mg, eGFR \>= 60 mL/min/1.73m\^2 or no confirmed decrease\>=20% from baseline and prednisone dose \<= 10 mg/d. Participant was considered as achieved CRR who did not discontinue study intervention for any reason excluding COVID-19 related discontinuations or met the medication intercurrent event (exceeded baseline glucocorticoid dose, increase above 10 mg/d prednisone equivalent after Week 12, use of new or increased dose of concomitant medication related to lupus nephritis (LN) or other immunosuppressive agents, within 8 weeks prior to the outcome measure time point (Week 24) or initiation of prohibited medications at any time prior to the outcome measure time point (Week 24).
Percentage of Participants With Treatment Failure (TF) Through Week 52 Up to Week 52 Percentage of participants with TF through Week 52 was reported. TF was defined as time to the first occurrence of TF from baseline. Participant was considered to have treatment failure, who did not continue study intervention for any reason excluding COVID-19 related discontinuations or met the medication intercurrent event (exceeded baseline glucocorticoid dose, increase above 10 mg/d prednisone equivalent after Week 12, use of new or increased dose of concomitant medication related to LN or other immunosuppressive agents, within 8 weeks prior to the outcome measure time point (Week 52) or initiation of prohibited medications at any time prior to the outcome measure time point (Week 52).
Number of Participants With Adverse Events (AEs) DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96) Number of participants with AEs were reported. An AE was defined as any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product did not necessarily have a causal relationship with the treatment. Therefore, it could be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product.
Number of Participants With Serious Adverse Events (SAEs) DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96) Number of Participants with SAEs were reported. An AE was defined as any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product did not necessarily have a causal relationship with the treatment. Therefore, it could be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important.
Number of Participants With Related AEs DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96) Number of participants with related AEs were reported. An AE was defined as any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product did not necessarily have a causal relationship with the treatment. Therefore, it could be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. Related AE was defined as the AE assessed by the investigator related to study agent.
Number of Participants With AEs Leading to Discontinuation of Study Intervention DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96) Number of participants with AEs leading to discontinuation of study intervention were reported.
Number of Participants With Infections DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96) Number of participants with infections as assessed by the investigator were reported.
Number of Participants With Serious Infections DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96) Number of participants with serious infections as assessed by the investigator were reported.
Number of Participants With Infections Requiring Oral or Parenteral Antimicrobial Treatment DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96) Number of participants with infections requiring oral or parenteral antimicrobial treatment planned to be were reported.
Number of Participants With AEs Temporally Associated With an Infusion DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96) Number of participants with AEs temporally (a reaction that occurred during or within 1 hour after infusion) associated with an infusion were reported. AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product does not necessarily have a causal relationship with the treatment. Therefore, it can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product.
Number of Participants With AEs With Injection-site Reactions DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96) Number of participants with injection-site reactions as assessed by the investigator were reported. An injection-site reaction is any adverse reaction at a SC study intervention injection-site.
Change From Baseline in Clinical Laboratory Parameter: Activated Partial Thromboplastin Time Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: activated partial thromboplastin time was reported.
Change From Baseline in Clinical Laboratory Parameter: Basophils Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: basophils was reported.
Change From Baseline in Clinical Laboratory Parameter: Eosinophils Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: eosinophils was reported.
Change From Baseline in Clinical Laboratory Parameter: Erythrocytes Mean Corpuscular Hemoglobin Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: erythrocytes mean corpuscular hemoglobin was reported.
Change From Baseline in Clinical Laboratory Parameter: Erythrocytes Mean Corpuscular Volume Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: erythrocytes mean corpuscular volume was reported.
Change From Baseline in Clinical Laboratory Parameter: Erythrocytes Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: erythrocytes was reported.
Change From Baseline in Clinical Laboratory Parameter: Hematocrit Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical Laboratory parameter: hematocrit was reported.
Change From Baseline in Clinical Laboratory Parameter: Hemoglobin Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: hemoglobin was reported.
Change From Baseline in Clinical Laboratory Parameter Leukocytes Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: leukocytes was reported.
Change From Baseline in Clinical Laboratory Parameter: Lymphocytes Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: lymphocytes was reported.
Change From Baseline in Clinical Laboratory Parameter: Monocytes Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: monocytes was reported.
Change From Baseline in Clinical Laboratory Parameter: Hematology Parameter: Segmented Neutrophils Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: segmented neutrophils was reported.
Change From Baseline in Clinical Laboratory Parameter: Platelets Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: platelets was reported.
Change From Baseline in Clinical Laboratory Parameter: Prothrombin International Normalized Ratio Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: prothrombin international normalized ratio was reported.
Change From Baseline in Clinical Laboratory Parameter: Prothrombin Time Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: prothrombin time was reported.
Change From Baseline in Clinical Laboratory Parameter: Reticulocytes/Erythrocytes Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory hematology parameter:reticulocytes/erythrocytes was reported.
Change From Baseline in Clinical Laboratory Parameter: Alanine Aminotransferase Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: alanine aminotransferase was reported.
Change From Baseline in Clinical Laboratory Parameter: Albumin Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: albumin was reported.
Change From Baseline in Clinical Laboratory Parameter: Alkaline Phosphatase Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: alkaline phosphatase was reported.
Change From Baseline in Clinical Laboratory Parameter: Aspartate Aminotransferase Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: aspartate aminotransferase was reported.
Change From Baseline in Clinical Laboratory Parameter: Bicarbonate Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: bicarbonate was reported.
Change From Baseline in Clinical Laboratory Parameter: Bilirubin Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: bilirubin was reported.
Change From Baseline in Clinical Laboratory Parameters: Calcium Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: calcium was reported.
Change From Baseline in Clinical Laboratory Parameter: Chloride Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: chloride was reported.
Change From Baseline in Clinical Laboratory Parameters: Cholesterol Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: cholesterol was reported.
Change From Baseline in Clinical Laboratory Parameter: Creatine Kinase Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: creatine kinase was reported.
Change From Baseline in Clinical Laboratory Parameter: Creatinine Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: creatinine was reported.
Change From Baseline in Clinical Laboratory Parameter: Protein Baseline (Week 0), Weeks 24 and 52 Change from baseline in clinical laboratory parameter: protein was reported.
Change From Baseline in Clinical Laboratory Parameter: Phosphate Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: phosphate was reported.
Change From Baseline in Clinical Laboratory Parameter: Sodium Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: sodium was reported.
Change From Baseline in Clinical Laboratory Parameters: Potassium Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: potassium was reported.
Change From Baseline in Clinical Laboratory Parameters: Urea Nitrogen Baseline (Week 0), Week 24, and Week 52 Change from baseline in clinical laboratory parameter: urea nitrogen was reported.
Change From Baseline in Clinical Laboratory Parameter: Glomerular Filtration Rate (GFR) From Creatinine Adjusted for Body Surface Area (BSA) Baseline (Week 0), Weeks 24 and 52 Change from baseline in clinical laboratory parameter: GFR from Creatinine Adjusted for BSA was reported.
Change From Baseline in Clinical Laboratory Parameter: Gamma Glutamyl and Transferase Lactate Dehydrogenase Baseline (Week 0), Weeks 24 and 52 Change from baseline in clinical laboratory parameter: gamma glutamyl transferase and lactate dehydrogenase were reported.
Change From Baseline in Clinical Laboratory Parameter: Glucose and Magnesium Baseline, Weeks 24, 52 Change from baseline in clinical laboratory parameter: glucose and magnesium were reported.
Change From Baseline in Chemistry Parameters: Protein/Creatinine Baseline, Weeks 24 and 52 Change from baseline in chemistry parameter: protein/creatinine was reported.
Change From Baseline in Clinical Laboratory Parameter: Urate Baseline, Weeks 24, 52 Change from baseline in clinical laboratory parameter: urate was reported.
Change From Baseline in Clinical Laboratory Parameter: Urine Protein Baseline (Week 0), Weeks 24 and 52 Change from baseline in clinical laboratory parameter: urine protein was reported.
Number of Participants With Maximum US National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Toxicity Grade (Grade 4) in Clinical Laboratory Parameters: Hematology and Chemistry DB period: From Week 0 up to 12 week safety follow-up (i.e., up to Week 60); LTE phase: From Week 52 up to LTE phase termination (i.e., up to Week 96) Number of participants with maximum US NCI-CTCAE toxicity grade (Grade 4) in clinical laboratory parameters: hematology and chemistry were reported. Toxicity were graded as Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
Percentage of Participants With Abnormal Vital Signs: Systolic and Diastolic Blood Pressure Up to Week 60 Percentage of participants with abnormal vital signs: Systolic and Diastolic blood pressure were reported.
Serum Concentration of Guselkumab Predose: Weeks 0,4,8,12,16,20,24, 36; Post-dose: Week 0 (1 hour after intravenous administration), Day 2, Week 52 and 60 Serum Concentration of guselkumab were reported.
Number of Participants With Treatment-boosted Anti-drug Antibodies (ADA) Response From Baseline (Week 0) through Week 24 and Week 60 Treatment-boosted ADA positive participants: participants who were positive at baseline and whose titers increased 2-fold at any time after treatment. Titer values were categorized as\<=1:10, 10 to 100, 100 to 1000, \>1000.
Trial Locations
- Locations (60)
Centro de Investigaciones Medicas Tucuman
🇦🇷San Miguel De Tucuman, Argentina
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
UC San Diego
🇺🇸La Jolla, California, United States
Medical Center LTD Health Clinic Department of Cardiology and Rheumatology
🇺🇦Vinnytsya, Ukraine
Instituto Medico Strusberg SA
🇦🇷Cordoba, Argentina
Hosp. Univ. Vall D Hebron
🇪🇸Barcelona, Spain
Instituto de Reumatologia - Ir Medical Center S.A.
🇦🇷Mendoza, Argentina
LLC German Clinic
🇷🇺St. Petersburg, Russian Federation
Hosp. Univ. A Coruna
🇪🇸A Coruña, Spain
Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán
🇲🇽Mexico City, Mexico
Med Research, Inc.
🇺🇸El Paso, Texas, United States
Clinica Privada Velez Sarsfield
🇦🇷Córdoba, Argentina
Unidad Reumatologica las Americas S.C.P.
🇲🇽Merida, Mexico
Multidisciplinary Medical Center of Odessa National Medical University
🇺🇦Odessa, Ukraine
LLC Medical Sanitary Part No. 157
🇷🇺Saint-Petersburg, Russian Federation
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego
🇵🇱Lodz, Poland
Municipal non-commercial enterprise of Kharkiv Regional Council Regional Clinical Hospital
🇺🇦Kharkiv, Ukraine
Medical Center 'Consylium Medical'
🇺🇦Kyiv, Ukraine
Orenburg State Medical University
🇷🇺Orenburg, Russian Federation
Communal Noncommercial Enterprise Cherkasy Regional Hospital of Cherkasy Regional Council
🇺🇦Cherkasy, Ukraine
Medical Center 'Ok Clinic' of International Institute of Clinical Research LLC
🇺🇦Kyiv, Ukraine
Kyiv Railway Clinical Hospital #2 Of Branch 'Health Center' Of The Company 'Ukrainian Railway'
🇺🇦Kyiv, Ukraine
Phramongkutklao Hospital and Medical College
🇹🇭Bangkok, Thailand
SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
🇺🇦Kyiv, Ukraine
Municipal Non-profit Enterprise 'Odesa Regional Clinical Hospital' Odesa Regional Council
🇺🇦Odessa, Ukraine
Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council
🇺🇦Ternopil, Ukraine
Medical Center LLC 'Modern Clinic'
🇺🇦Zaporizhzhya, Ukraine
Songklanagarind hospital
🇹🇭Hat Yai, Thailand
Instituto Médico de la Fundación de Estudios Clínicos (ECLIN)
🇦🇷Rosario, Argentina
Medvin Clinical Research
🇺🇸Covina, California, United States
Academic Medical Research Institute
🇺🇸Los Angeles, California, United States
University of Florida College of Medicine
🇺🇸Gainesville, Florida, United States
The Feinstein Institute for Medical Research
🇺🇸Manhasset, New York, United States
NYU Langone Ambulatory Care Brooklyn Heights
🇺🇸Brooklyn, New York, United States
Centro Médico Reumatológico (OMI)
🇦🇷Buenos Aires, Argentina
Hospital Ramos Mejia
🇦🇷Caba, Argentina
ARCIS Salud SRL Aprillus asistencia e investigacion
🇦🇷Caba, Argentina
Unidad de Investigaciones Reumatologicas A.C
🇲🇽San Luis Potosi, Mexico
Consultorio de Reumatologia
🇲🇽Mexico, Mexico
Uniwersyteckie Centrum Medyczne, Klinika Nefrologii, Transplantologii i Chorób Wewnętrznych
🇵🇱Gdansk, Poland
LLL Medical Center Revma-Med
🇷🇺Kemerovo, Russian Federation
Uniwersytecki Szpital Kliniczny we Wrocławiu
🇵🇱Wroclaw, Poland
Hosp. Univ. Ramon Y Cajal
🇪🇸Madrid, Spain
Saratov Regional Clinical Hospital
🇷🇺Saratov, Russian Federation
Kaohsiung Veterans General Hospital
🇨🇳Kaohsiung, Taiwan
Hosp. Univ. Infanta Leonor
🇪🇸Madrid, Spain
Hosp. Univ. de Basurto
🇪🇸Bilbao, Spain
China Medical University Hospital
🇨🇳Taichung, Taiwan
Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
Hosp. Univ. Fuenlabrada
🇪🇸Madrid, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Hosp. Clinico Univ. de Valencia
🇪🇸Valencia, Spain
Hospital Civil de Guadalajara Fray Antonio Alcalde
🇲🇽Guadalajara, Mexico
Maharaj Nakorn Chiangmai Hospital
🇹🇭Chiang Mai, Thailand
Centro de Investigacion y Tratamiento Reumatologico S C
🇲🇽Ciudad de Mexico, Mexico
Ramathibodi Hospital
🇹🇭Bangkok, Thailand
City Clinical Hospital No. 2
🇺🇦Kryvyi Rih, Ukraine
State Institution 'Institute of Nephrology of the National Academy of Medical Sciences of Ukraine'
🇺🇦Kyiv, Ukraine
MNPE 'Vinnytsia Regional Clinical Hospital named after M.I. Pyrogov of Vinnytsia Regional Council'
🇺🇦Vinnytsia, Ukraine