A Study To Evaluate Efficacy, Safety, Pharmacokinetics, And Pharmacodynamics Of Satralizumab In Patients With Generalized Myasthenia Gravis
- Conditions
- Generalized Myasthenia Gravis
- Interventions
- Other: Placebo
- Registration Number
- NCT04963270
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of satralizumab compared with placebo in participants with generalized myasthenia gravis (gMG).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 188
- Signed Informed Consent Form
- For adolescent patients: Informed Consent Form for study participation signed by the parents or a legal guardian, and patient assent obtained, as per local requirements
- Ability to comply with the study protocol procedures
- Confirmed diagnosis of gMG (anti-AChR, anti-MuSK or anti-LRP4 present at screening)
- A total MG-ADL score of ≥ 5 points at screening with more than 50% of this score attributed to non-ocular items
- MGFA severity Class II-IV
- Ongoing gMG treatment at a stable dose
- For female patients of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for at least 3 months after the final dose of satralizumab.
- History of thymectomy within 12 months prior to screening
- Ocular MG (MGFA Class I) and myasthenic crisis (MGFA Class V) within the last 3 months prior to screening
- Known disease other than gMG that would interfere with the course and conduct of the study
- Positive screening tests for hepatitis B virus (HBV) and hepatitis C virus (HCV)
- Evidence of latent or active tuberculosis (excluding patients receiving chemoprophylaxis for latent tuberculosis infection)
- Receipt of live or live attenuated vaccine within 6 weeks prior to baseline
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the last dose
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants will receive placebo at Weeks 0, 2, 4, and Q4W thereafter Satralizumab Satralizumab Participants will receive Satralizumab at Weeks 0, 2, 4, and Q4W thereafter. Adolescent patients who first enter the study in the OLE period will receive satralizumab SC loading doses at Week 0, 2, and 4 in the OLE, followed by maintenance doses Q4W thereafter and will remain on stable background therapy until Week 24 of the OLE.
- Primary Outcome Measures
Name Time Method DB Period: Mean Change From Baseline in Total Myasthenia Gravis Activities of Daily Living (MG-ADL) Score in the AChR+ Population At Week 24 The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
- Secondary Outcome Measures
Name Time Method DB Period: Mean Change From Baseline in QMG Score in OP at Week 24 At Week 24 The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity.
DB Period: Mean Change From Baseline in Total MG-ADL Score in the Overall Population (OP) at Week 24 At Week 24 The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in AChR+ Population at Week 24 At Week 24 The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. Participants who received rescue therapy were considered non-responders.
DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in OP at Week 24 At Week 24 The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. Participants who received rescue therapy were considered non-responders.
DB Period: Mean Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score in AChR+ Population at Week 24 At Week 24 The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity.
DB Period: Mean Change From Baseline in Myasthenia Gravis Quality of Life 15 Scale (Revised) (MG-QOL 15r) Total Score in AChR+ Population at Week 24 At Week 24 The MG-QOL-15r is a disease-specific health-related QoL measure that consists of 15 items: mobility (9 items), symptoms (3 items), and contentment and emotional well-being (3 items). Items were scored on a scale from 0=Not at all to 2=Very much with the total score ranging from 0 to 30 and higher scores indicate worse health-related quality of life (HRQoL).
DB Period: Mean Change From Baseline in MG-QOL 15r Total Score in OP at Week 24 At Week 24 The MG-QOL-15r is a disease-specific health-related QoL measure that consists of 15 items: mobility (9 items), symptoms (3 items), and contentment and emotional well-being (3 items). Items are scored on a scale from 0=Not at all to 2=Very much, with the total score ranging from 0 to 30 and higher scores indicate worse HRQoL.
DB Period: Mean Change From Baseline in Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue Subscale Total Score in AChR+ Population at Week 24 At Week 24 The Neuro-QoL is a validated tool designed to evaluate the HRQoL in participants with chronic neurological disease. The Fatigue Subscale is implemented as an eight-item, stand-alone short form that assesses the multi-dimensional aspects of fatigue ranging from general tiredness to debilitating exhaustion that Impacts activities of daily living. Each item was assessed using a 5-level Likert scale ranging between 1=never to 5=always. Raw scores range from 8 to 40, higher values indicate greater fatigue.
DB Period: Mean Change From Baseline in Neuro-QoL Fatigue Subscale Total Score in OP at Week 24 At Week 24 The Neuro-QoL is a validated tool designed to evaluate the HRQoL in participants with chronic neurological disease. The Fatigue Subscale is implemented as an eight-item, stand-alone short form that assesses the multi-dimensional aspects of fatigue ranging from general tiredness to debilitating exhaustion that Impacts activities of daily living. Each item was assessed using a 5-level Likert scale ranging between 1=never to 5=always. Raw scores range from 8 to 40, higher values indicate greater fatigue.
DB Period: Mean Change From Baseline in Total Myasthenia Gravis Composite (MGC) Score in AChR+ Population at Week 24 At Week 24 The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity.
DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in AChR+ Population at Week 24 At Week 24 The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity.
DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in OP at Week 24 At Week 24 The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity.
DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in AChR+ Population at Week 24 At Week 24 The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity.
DB Period: Mean Change From Baseline in Total MGC Score in OP at Week 24 At Week 24 The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity.
DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG-ADL Score of 0 or 1) in OP at Week 24 At Week 24 The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
DB Period: Percentage of Participants With at Least One gMG-Related Exacerbation Between Baseline and Week 24 in OP Baseline up to Week 24 gMG-related exacerbation was defined as one of the following: MG crisis; Substantial symptomatic worsening that requires immediate therapy; or health in jeopardy if rescue therapy is not given.
DB Period: Duration of Meaningful Improvement, Defined as ≥ 2-Point Reduction From Baseline in Total MG-ADL Score in OP Baseline, Week 24 The duration was the difference in weeks between the two visits defining the start and end (or Week 24) of reduction from baseline. The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
DB Period: Number of Participants With Adverse Events (AEs) Day 1 up to approximately 24 weeks An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptoms, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product.
DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in OP at Week 24 At Week 24 The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity.
DB Period: Percentage of Participants in OP Receiving Rescue Therapy Between Baseline and Week 24 Baseline up to Week 24 The percentage of participants receiving rescue therapy during DBP analyzed the variable that encodes whether a participant received rescue therapy during DBP or not. If a participant stopped the study drug but received rescue therapy during the safety follow-up and this occurred within 24 weeks of baseline then this was counted as having received rescue therapy.
DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG-ADL Score of 0 or 1) in AChR+ Population at Week 24 At Week 24 The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
DB Period: Percentage of Participants With at Least One gMG-Related Exacerbation Between Baseline and Week 24 in AChR+ Population Baseline up to Week 24 gMG-related exacerbation was defined as one of the following: MG crisis; Substantial symptomatic worsening that requires immediate therapy; or health in jeopardy if rescue therapy is not given.
DB Period: Percentage of Participants in AChR+ Population Receiving Rescue Therapy Between Baseline and Week 24 Baseline up to Week 24 The percentage of participants receiving rescue therapy during DBP analyzed the variable that encodes whether a participant received rescue therapy during DBP or not. If a participant stopped the study drug but received rescue therapy during the safety follow-up and this occurred within 24 weeks of baseline then this was counted as having received rescue therapy.
Number of Participants With Anti-drug Antibodies (ADAs) to Satralizumab Baseline to Week 24 The percentage of ADA-positive participants after drug administration were determined for participants exposed to satralizumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result. Participants were considered to be ADA-negative if they were ADA-negative or had missing data at baseline and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that is at least 4-fold (0.60 titer unit) greater than the titer of the baseline sample.
DB Period: Duration of Meaningful Improvement, Defined as ≥ 2-Point Reduction From Baseline in Total MG-ADL Score in AChR+ Population Baseline, Week 24 The duration was the difference in weeks between the two visits defining the start and end (or Week 24) of reduction from baseline. The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24 DB Period: Serum Levels of Interleukin-6 (IL-6) Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24 Serum Concentrations of Satralizumab Weeks 0, 2, 4, 8, 12, 16, 20 and 24
Trial Locations
- Locations (76)
Prairie Education and Research
🇺🇸O'Fallon, Illinois, United States
Hospital Italiano
🇦🇷Caba, Argentina
Hospital Ramos Mejía
🇦🇷Caba, Argentina
Hospital Britanico
🇦🇷Ciudad Autonoma Bs As, Argentina
Fundación Scherbovsky
🇦🇷Mendoza, Argentina
INECO Neurociencias Orono
🇦🇷Rosario, Argentina
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Hospital das Clinicas - UNICAMP
🇧🇷Campinas, São Paulo, Brazil
Sir Run Run Shaw Hospital
🇨🇳Hangzhou, China
The First Affiliated Hospital Of Shandong First Medical University
🇨🇳Jinan, China
CHU Bordeaux
🇫🇷Bordeaux cedex, France
APHP Raymond Poincare
🇫🇷Garches, France
Hopital Timone Adultes
🇫🇷Marseille, France
CHU de Nantes - Hotel Dieu
🇫🇷Nantes, France
St. Josef-Hospital, Klinik für Neurologie
🇩🇪Bochum, Germany
Universitätsklinikum Essen (AöR)
🇩🇪Essen, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
A.R.N.A.S. Civico Di Cristina Benfratelli
🇮🇹Palermo, Sicilia, Italy
Ospedale Cà Foncello
🇮🇹Treviso, Veneto, Italy
St. Marianna University Hospital
🇯🇵Kanagawa, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Osaka University Hospital
🇯🇵Suita, Japan
Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Klinika Neurologii Doros?ych, Uniwersyteckie Centrum Kliniczne
🇵🇱Gda?sk, Poland
Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K
🇵🇱Krakow, Poland
Novosibirsk State Regional Clinical Hospital
🇷🇺Novosibirsk, Russian Federation
Clinica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitario la Fe
🇪🇸Valencia, Spain
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
The Affiliated Hospital of Guizhou Medical University
🇨🇳Guiyang, China
Children's Hospital of Fudan University
🇨🇳Shanghai, China
Aarhus Universitetshospital
🇩🇰Aarhus N, Denmark
Azienda Ospedaliera A. Cardarelli
🇮🇹Napoli, Campania, Italy
Juntendo University Hospital
🇯🇵Bunkyo-ku, Japan
Seirei Hamamatsu General Hospital
🇯🇵Shizuoka, Japan
Rigshospitalet
🇩🇰København Ø, Denmark
CHU Nice - Hôpital Pasteur 2
🇫🇷Nice, France
Chiba University Hospital
🇯🇵Chiba-shi, Chiba, Japan
University of Chicago Hospital
🇺🇸Chicago, Illinois, United States
The First Hospital of Jilin University
🇨🇳Changchun City, China
West China Hospital - Sichuan University
🇨🇳Chengdu City, China
Keck School of Medicine of USC
🇺🇸Los Angeles, California, United States
University of California Irvine - Manchester Pavilion
🇺🇸Orange, California, United States
SC3 Research Group, Inc
🇺🇸Pasadena, California, United States
Medical Faculty Associates Inc.
🇺🇸Washington, District of Columbia, United States
Pusan National University Yangsan Hospital
🇰🇷Gyeongsangnam-do, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Zespol Poradni Specjalistycznych - Poradnia Neurologiczna
🇵🇱Kraków, Poland
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Faculdade de Medicina do ABC - FMABC
🇧🇷Santo Andre, São Paulo, Brazil
Hospital Sao Paulo
🇧🇷Sao Paulo, São Paulo, Brazil
MUCH - Montreal Neurological Institute & Hospital
🇨🇦Montreal, Quebec, Canada
Beijing Tongren Hospital
🇨🇳Beijing, China
Beijing Tiantan Hospital,Capital Medical University
🇨🇳Beijing, China
Huashan Hospital, Fudan University
🇨🇳Shanghai City, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, China
Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan City, China
Tangdu Hospital
🇨🇳Xi'an City, China
Fond. Istituto Neurologico C.Besta
🇮🇹Milano, Lombardia, Italy
General Hanamaki Hospital
🇯🇵Hanamaki, Iwate, Japan
NHO Hokkaido Medical Center
🇯🇵Hokkaido, Japan
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
🇵🇱Lublin, Poland
Taipei Veterans General Hospital-Neurology
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation Linkou Branch
🇨🇳Taoyuan City, Taiwan
Ondokuz Mayis Univ. Med. Fac.
🇹🇷Samsun, Turkey
Sapporo Medical University Hospital
🇯🇵Hokkaido, Japan
International University of Health and Welfare Narita Hospital
🇯🇵Narita, Chiba, Japan
Tokyo Medical And Dental University, Medical Hospital
🇯🇵Tokyo, Japan
Krasnoyarsk State Medical Academy
🇷🇺Krasnoyarsk, Krasnojarsk, Russian Federation
Hospital Universitari de Bellvitge
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Ege University Medical Faculty
🇹🇷Izmir, Turkey
Kocaeli University Hospital
🇹🇷Kocaeli, Turkey