Study to Evaluate Tezepelumab in Adults With Chronic Spontaneous Urticaria

Phase 2

Completed

Conditions: Chronic Spontaneous Urticaria

Interventions: Biological: Omalizumab
Biological: Tezepelumab Dose 1
Biological: Placebo
Biological: Tezepelumab Dose 2

Registration Number: NCT04833855

Lead Sponsor: Amgen

Brief Summary: The primary objective of this study is to evaluate the effect of tezepelumab on improvement in the Urticaria Activity Score over 7 days (UAS7).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 183

Inclusion Criteria

Signed informed consent must be obtained prior to participation in the study.
Male and female participants ≥ 18 years and ≤ 80 years of age at the time of screening.
Chronic spontaneous urticaria (CSU) diagnosis for ≥ 6 months at the time of screening.
CSU inadequately controlled by second generation H1-antihistamines (sgAH) at enrollment, as defined by all of the following:
The presence of itch and hives for >= 6 consecutive weeks at any time prior to screening visit 2
Failure to respond to an sgAH (up to 4 times the approved dose)
Urticaria Activity Score over 7 days (UAS7) (range 0-42) >= 16 and Hives Severity Score over 7 days (HSS7) (range 0-21) >= 8 during the 7 days prior to enrollment
Participant with CSU who discontinued, is intolerant to, or was an inadequate responder to anti-IgE therapies despite being treated with omalizumab 300 mg every 4 weeks (Q4W) for 6 months or higher doses of omalizumab > 2 months or another anti-IgE therapy. Note: This criterion is only applicable for anti-IgE-experienced participants.
Participant willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedules.
Subject must have been on a sgAH at approved or increased doses (up to 4x the approved dose) for treatment of CSU for at least 3 consecutive days immediately prior to the day -14 screening visit (screening visit 2) and must have documented current use on the day of screening visit 1

Exclusion Criteria

Disease related, including but not limited to:

Urticaria is solely due to inducible urticaria
Active dermatologic diseases (or conditions) other than chronic urticaria, with urticaria wheals or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency)
Any other active skin disease associated with chronic itching that might influence, in the investigator's opinion, the study evaluations and results (eg, atopic dermatitis, dermatitis herpetiformis, senile pruritus, etc.)
History of a clinically significant infection within 28 days prior to day 1 that, in the opinion of the investigator or medical monitor, might compromise the safety of the participant in the study, interfere with evaluation of the investigational product, or reduce the participants ability to participate in the study.
Evidence of active tuberculosis (TB) (in the opinion of the investigator), either treated or untreated, or a positive purified protein derivative (PPD) or QuantiFERON-TB Gold Plus (QFT-Plus) test for TB during screening.
History of malignancy, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy ≥ 12 months prior to screening or other malignancies treated with apparent success with curative therapy ≥ 5 years prior to screening visit 1.
Subject is unable to complete an electronic patient diary or complete questionnaires, or does not meet the required level of compliance with the eDiary during the 14 days sgAH stabilization period

Other medical conditions

History or evidence of severe depression, schizophrenia, previous suicide attempts, or suicidal ideation.

Prior/concomitant therapy, including but not limited to:

Treatment with any biologic products (eg, omalizumab, ligelizumab) within 4 months or 5 half-lives (whichever is longer) prior to screening visit 1
Routine (daily or every other day for 5 or more consecutive days) use of systemic corticosteroids, systemic hydroxychloroquine, methotrexate, cyclosporine A, cyclophosphamide, tacrolimus, azathioprine, and mycophenolate mofetil within 30 days prior to screening visit 1.
Major surgery within 8 weeks prior to screening visit 1 or planned inpatient surgery or hospitalization during the study period.
Receipt of Ig or blood products within 30 days prior to screening visit 1.
Vaccination with a live or attenuated vaccine within 30 days prior to screening visit 1. Receipt of COVID-19 vaccines and inactive/killed vaccinations (eg, inactive influenza) are allowed, provided the vaccinations are not administered within 7 days before or after any study dosing visit.
Known hypersensitivity, including severe hypersensitivity reactions and/or history of anaphylactic shock, to any of the products or components to be administered during dosing or to products of similar chemical classes (ie, to murine, chimeric, or human antibodies.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: Omalizumab	Omalizumab	Participants naive to anti-IgE therapies will receive omalizumab.
Group 3: Tezepelumab Dose 1	Tezepelumab Dose 1	Participants naive to anti-IgE therapies will receive tezepelumab.
Group 2: Placebo	Placebo	Participants naive to anti-IgE therapies will receive a placebo.
Group 4: Tezepelumab Dose 2	Tezepelumab Dose 2	Participants naive to anti-IgE therapies will receive tezepelumab.
Group 5: Placebo	Placebo	Participants previously treated with anti-IgE therapies will receive a placebo.
Group 6: Tezepelumab Dose 1	Tezepelumab Dose 1	Participants previously treated with anti-IgE therapies will receive tezepelumab.
Group 7: Tezepelumab Dose 2	Tezepelumab Dose 2	Participants previously treated with anti-IgE therapies will receive tezepelumab.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Week 16	Baseline and Week 16	The UAS is a CSU-specific patient-reported outcome measure with 2 components: Hives Severity Score (HSS) for number of wheals and an Itch Severity Score (ISS) for itch intensity, and are each scored from 0 (no wheals, no itch) to 3 (\>50 wheals, severe itch) for the previous 24 hours. The HSS and ISS are combined to give a daily UAS ranging from 0 to 6. The sum of the daily UAS over a 7-day period provides the UAS7, from 0 (no symptoms) to 42 (severe urticaria). The least squares mean (LSM) estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline UAS7, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in urticaria activity.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With a Change From Baseline in HSS7 of ≤ -5.5 (Minimal Important Difference)	Baseline and Week 16	The sum of daily HSS over a 7-day period provides the HSS7, from 0 (no symptoms) to 21 (severe wheals). Minimal important difference in HSS7 was defined as a change from baseline of ≤ -5.5.
Change From Baseline in ISS Over 7 Days (ISS7) at Week 16	Baseline and Week 16	The ISS is a component of the UAS, a CSU-specific patient-reported outcome measure and assessed itch intensity, with daily scores ranging from 0 (no itch) to 3 (severe itch) for the previous 24 hours. The sum of daily ISS over a 7-day period provides the ISS7, from 0 (no symptoms) to 21 (severe itch). The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline ISS7, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in urticaria activity.
Number of Participants With a Change From Baseline in UAS7 of ≤ -10 (Minimal Important Difference)	Baseline and Week 16	The sum of the daily UAS over a 7-day period provides the UAS7, from 0 (no symptoms) to 42 (severe urticaria). Minimal important difference in UAS7 was defined as a change from baseline of ≤ -10.
Number of Participants With a UAS7 of ≤ 6 (Minimal Residual Disease) at Week 16	Week 16	The sum of the daily UAS over a 7-day period provides the UAS7, from 0 (no symptoms) to 42 (severe urticaria). Minimal residual disease in UAS7 was defined as a score ≤ 6 and indicates well-controlled urticaria and a good response to treatment.
Number of Participants With a Change From Baseline in ISS7 of ≤ -5 (Minimal Important Difference)	Baseline and Week 16	The sum of daily ISS over a 7-day period provides the ISS7, from 0 (no symptoms) to 21 (severe itch). Minimal important difference in ISS7 was defined as a change from baseline of ≤ -5.
Number of Cumulative Days of sgAH Rescue Medication Use From Baseline to Week 16	Baseline to Week 16	Participants recorded any need of sgAH rescue medication in their daily electronic diary.
Serum Concentration of Tezepelumab	Week 1 pre-dose, Weeks 2, 4, 8, 12, 16, 24, and 32	The lower limit of quantification was 10 ng/mL, and values below this limit were set to zero.
Change From Baseline in HSS Over 7 Days (HSS7) at Week 16	Baseline and Week 16	The HSS is a component of the UAS, a CSU-specific patient-reported outcome measure and assessed the number of wheals, with daily scores ranging from 0 (no wheals) to 3 (\>50 wheals) for the previous 24 hours. The sum of daily HSS over a 7-day period provides the HSS7, from 0 (no symptoms) to 21 (severe wheals). The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline HSS7, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in urticaria activity.
Number of Participants With ISS7 = 0 at Week 16 (Complete Resolution)	Week 16	The sum of daily ISS over a 7-day period provides the ISS7, from 0 (no symptoms) to 21 (severe itch). An ISS7 = 0 indicates a complete resolution of itch.
Change From Baseline in SQS7: Sum of Average Daily Q1 - Q3 at Week 16	Baseline and Week 16	The SQS was assessed by the participant through 3 questions relating to falling asleep (Q1), wakefulness (Q2), and feeling rested in the morning (Q3). The sum of average daily Q1 - Q3 score was generated by averaging 3 daily sleep quality items and then summing the daily average over 7 days with a score ranging from 0 (good quality sleep) to 21 (poor quality sleep) (sum of the average daily Q1 - Q3). The LSM estimates were based on the repeated measure model with stratification factor (prior anti-IgE status), baseline SQS7 - sum of average daily Q1 - Q3, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in sleep quality.
Change From Baseline in Weekly Angioedema Activity Score (AAS7) at Week 16	Baseline and Week 16	The AAS is a 5-item patient-reported outcome measure used to determine angioedema activity. Participants retrospectively documented the presence or absence of angioedema in the past 24 hours, and the AAS daily score ranged from 0 to 15 points, assessing 5 key factors when angioedema is present, including duration, physical discomfort, impact on daily activities, impact on appearance, and overall severity). The daily AAS scores are summed for 7 days to form the AAS7 with a range of 0 (not present) to 105 (most severe angioedema activity). Negative changes from baseline indicate an improvement in angioedema activity. The LSM estimates were based on the repeated measure model with stratification factor (prior anti-IgE status), baseline AAS7, treatment, study week and the interaction between treatment and study week.
Number of Participants With an AECT Score = 16 at Week 16 (Complete Control)	Baseline and Week 16	The total AECT score ranges from 0 to 16, with higher scores indicating better controlled disease. Complete control was defined as AECT score = 16.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Day 1 Week 1 to Week 32, up to 32 weeks	An adverse event (AE) was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with study treatment. TEAEs were AEs that started on or after the first dose of investigational product up to the end of study (Week 32). A serious AE (SAE) was defined as any untoward medical occurrence that met at least 1 of the following serious criteria: immediately life-threatening, required hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other medically important serious event.
Change From Baseline in the Angioedema Quality of Life Questionnaire (AE-QoL) at Week 16	Baseline and Week 16	The AE-QoL is a validated angioedema QoL questionnaire for participants with angioedema. It consists of 17 questions evaluating 4 domains including functioning, fatigue/mood, fear/shame, and food with a recall period of 4 weeks. The total score is transformed to a linear scale ranging from 0 to 100, with a higher score indicating a worse impairment in QoL. A negative change from baseline indicates an improvement in QoL. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline AE-QoL score, treatment, study week and the interaction between treatment and study week.
Number of Participants With a UAS7 = 0 at Week 16 (Complete Response)	Week 16	The sum of the daily UAS over a 7-day period provides the UAS7, from 0 (no symptoms) to 42 (severe urticaria). A complete response was defined as UAS7 = 0 at Week 16.
Number of Participants With HSS7 = 0 at Week 16 (Complete Resolution)	Week 16	The sum of daily HSS over a 7-day period provides the HSS7, from 0 (no symptoms) to 21 (severe wheals). An HSS7 = 0 indicates a complete resolution of hives.
Change From Baseline in Weekly Sleep Quality Score (SQS7): Sum of Daily SQS at Week 16	Baseline and Week 16	The SQS was assessed by the participant through 3 questions relating to falling asleep (Q1), wakefulness (Q2), and feeling rested in the morning (Q3). The sum of the 3 daily sleep quality items over 7 days, ranged from 0 (good quality sleep) to 63 (poor quality sleep). The LSM estimates were based on the repeated measure model with stratification factor (prior anti-IgE status), baseline SQS7 - sum of SQS, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in sleep quality.
Change From Baseline in Urticaria Control Test (UCT) Score at Week 16	Baseline and Week 16	The UCT assesses disease control in participants with CSU through a retrospective validated scoring system, evaluating the physical symptoms of chronic urticaria (itch, hives and/or angioedema) and the effectiveness of treatment over 4 weeks. It consists of 4 questions with 5 answer options, scored from 0 to 4, and the UCT score is the sum of all 4 questions, with total score ranging from 0 (no control) to 16 (complete control). A score of ≥ 12 indicates well-controlled urticaria and a score of ≤ 11 points indicates poor disease control. A positive change from baseline indicates an improvement in disease control. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline UCT score, treatment, study week and the interaction between treatment and study week.
Change From Baseline in Weekly Sleep Interference Score (SIS7) at Week 16	Baseline and Week 16	The SIS is part of the Urticaria Patient Daily Diary and was assessed by the participant using the electronic diary once daily in the morning. Participants scored sleep interference on a scale of 0 (no interference) to 3 (substantial, woke up often, severe interference with sleep). The SIS7 was a sum of the daily scores over 7 days ranging from 0 to 21. The LSM estimates were based on the repeated measure model with stratification factor (prior anti-IgE status), baseline SIS7, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in sleep interference.
Number of Cumulative Weeks That Participants Achieved AAS7 = 0 at Week 16 (Angioedema Occurrence Free)	Baseline to Week 16	The AAS is a 5-item patient-reported outcome measure used to determine angioedema activity. Participants retrospectively documented the presence or absence of angioedema in the past 24 hours, and the AAS daily score ranged from 0 to 15 points, assessing 5 key factors when angioedema is present, including duration, physical discomfort, impact on daily activities, impact on appearance, and overall severity). The daily AAS scores are summed for 7 days to form the AAS7 with a range of 0 (not present) to 105 (most severe angioedema activity). Angioedema occurrence free was defined as AAS7 = 0.
Change From Baseline in the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Week 16	Baseline and Week 16	The CU-Q2oL is a 23-item, self-reported urticaria-specific measure to evaluate 6 dimensions of quality of life (QoL): pruritus, impact on life activities, sleep problems, limitations, looks, and swelling. The total score is transformed to a linear scale of 0 to 100 with a higher CU-Q2oL score indicating a higher QoL impairment. A negative change from baseline indicates an improvement in QoL. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline CU-Q2oL score, treatment, study week and the interaction between treatment and study week.
Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16	Baseline and Week 16	The DLQI is a 10-item, participant-completed, health-related QoL assessment with content specific to those with dermatology conditions. The DLQI evaluates participant perceptions including dermatology-related symptoms and feelings, impacts on daily activities, leisure, work or school, personal relationships, and side effects of treatment. The recall period was 1 week. The DLQI total score ranges from 0 to 30 with a higher score indicating a greater QoL impairment. A negative change from baseline indicates an improvement in QoL. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline DLQI score, treatment, study week and the interaction between treatment and study week.
Change From Baseline in the Angioedema Control Test (AECT) Score at Week 16	Baseline and Week 16	The AECT is a patient-reported outcome measure to evaluate disease control in the domains of signs and symptoms, QoL, anxiety/fear, and effectiveness of therapy. The total AECT score ranges from 0 to 16, with higher scores indicating well-controlled disease. A positive change from baseline indicates an improvement in angioedema control. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline AECT score, treatment, study week and the interaction between treatment and study week.
Change From Baseline in the Work Productivity and Activity Impairment Questionnaire: Chronic Urticaria (WPAI-CU) Score at Week 16	Baseline and Week 16	The WPAI-CU is a questionnaire that assesses the impact of an intervention on work productivity, evaluating 4 areas including absenteeism, presenteeism, work productivity loss, and activity impairment over the past 7 days. Each of the areas is scored separately as a percentage, ranging from 0 to 100, with higher numbers indicating greater impairment and less productivity. A negative change from baseline indicates an improvement. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline WPAI-CU score, treatment, study week and the interaction between treatment and study week.

Trial Locations

Locations (81): Jonathan Corren MD Inc
🇺🇸
Los Angeles, California, United States
Dermatology Research Associates
🇺🇸
Los Angeles, California, United States
Gordon Sussman Clinical Research Incorporated
🇨🇦
North York, Ontario, Canada
Lynderm Research Inc
🇨🇦
Markham, Ontario, Canada
Centre Hospitalier Universitaire Archet 2
🇫🇷
Nice, France
Universitaetsklinikum Dresden
🇩🇪
Dresden, Germany
Cheema Research Incorporated
🇨🇦
Mississauga, Ontario, Canada
Dr. S. K. Siddha Medicine Professional Corporation
🇨🇦
Newmarket, Ontario, Canada
Andreas Syggros Hospital
🇬🇷
Athens, Greece
Clinical Research Center of Alabama
🇺🇸
Birmingham, Alabama, United States
Avance Clinical Trials
🇺🇸
Laguna Niguel, California, United States
Allergy Research Canada Incorporated
🇨🇦
Niagara Falls, Ontario, Canada
Clinique Spécialisée en Allergie de la Capitale
🇨🇦
Quebec, Canada
Centre Hospitalier Universitaire de Brest - Hôpital Morvan
🇫🇷
Brest, France
Centre Hospitalier Universitaire de Grenoble - Hopital Nord Michallon
🇫🇷
Grenoble Cedex 9, France
Hôpital Saint Eloi
🇫🇷
Montpellier cedex 5, France
Johannes Gutenberg Universitaet Mainz
🇩🇪
Mainz, Germany
Centre Hospitalier Lyon Sud
🇫🇷
Pierre Benite Cedex, France
Laiko General Hospital of Athens
🇬🇷
Athens, Greece
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
🇮🇹
Milano, Italy
Azienda Ospedaliero Universitaria di Modena
🇮🇹
Modena, Italy
Osaka Habikino Medical Center
🇯🇵
Habikino-shi, Osaka, Japan
Nihon University Itabashi Hospital
🇯🇵
Itabashi-ku, Tokyo, Japan
Icahn School of Medicine at Mount Sinai
🇺🇸
New York, New York, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Wojskowy Instytut Medyczny
🇵🇱
Warszawa, Poland
The Allergy Asthma and Sinus Center, East Tennessee Center for Clinical Research
🇺🇸
Knoxville, Tennessee, United States
Clinical Research Center Spzoo Medic-R Spolka Komandytowa
🇵🇱
Poznan, Poland
Dermatology Research Institute Incorporated
🇨🇦
Calgary, Alberta, Canada
Dermatology and Ophthalmology Kume Clinic
🇯🇵
Sakai-shi, Osaka, Japan
AMICARE z ograniczona odpowiedzialnoscia spolka komandytowa
🇵🇱
Lodz, Poland
Kliniczny Szpital Wojewodzki nr 1 im Fryderyka Chopina
🇵🇱
Rzeszow, Poland
George Papageorgiou General Hospital of Thessaloniki
🇬🇷
Thessaloniki, Greece
Sotiria General Hospital
🇬🇷
Athens, Greece
Attikon University General Hospital of Athens
🇬🇷
Athens, Greece
Hiroshima University Hospital
🇯🇵
Hiroshima-shi, Hiroshima, Japan
Brunswick Dermatology Centre
🇨🇦
Fredericton, New Brunswick, Canada
Fondazione Policlinico Tor Vergata
🇮🇹
Roma, Italy
IRCCS Istituto Clinico Humanitas
🇮🇹
Rozzano MI, Italy
First OC Dermatology
🇺🇸
Fountain Valley, California, United States
Asthma and Allergy Associates PC
🇺🇸
Colorado Springs, Colorado, United States
Clinical Science Institute
🇺🇸
Santa Monica, California, United States
Dawes Fretzin Clinical Research Group, LLC
🇺🇸
Indianapolis, Indiana, United States
Bluegrass Allergy Care
🇺🇸
Lexington, Kentucky, United States
Advanced Medical Research PC
🇺🇸
Sandy Springs, Georgia, United States
The Community Research of South Florida
🇺🇸
Miami Lakes, Florida, United States
David Fivenson MD Professional Liability Company
🇺🇸
Ann Arbor, Michigan, United States
Epiphany Dermatology of Kansas, LLC
🇺🇸
Overland Park, Kansas, United States
Clarkston Skin Research
🇺🇸
Clarkston, Michigan, United States
Family Allergy and Asthma Research Institute
🇺🇸
Louisville, Kentucky, United States
Johns Hopkins Asthma and Allergy Center
🇺🇸
Baltimore, Maryland, United States
Bernstein Clinical Research Center LLC
🇺🇸
Cincinnati, Ohio, United States
Aventiv Research Inc
🇺🇸
Dublin, Ohio, United States
Clinical Partners LLC
🇺🇸
Johnston, Rhode Island, United States
Cutis Wellness Dermatology and Dermatopathology, PLLC
🇺🇸
Laredo, Texas, United States
Suzanne Bruce and Associates
🇺🇸
Houston, Texas, United States
LEADER Research
🇨🇦
Hamilton, Ontario, Canada
*Charité*
🇩🇪
Berlin, Germany
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
🇮🇹
Torino, Italy
Fujita Health University Bantane Hospital
🇯🇵
Nagoya-shi, Aichi, Japan
Policlinico Universitario Agostino Gemelli
🇮🇹
Roma, Italy
Takagi Dermatological Clinic
🇯🇵
Obihiro-shi, Hokkaido, Japan
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷
Seongnam-si, Gyeonggi-do, Korea, Republic of
Nomura Dermatology Clinic
🇯🇵
Yokohama-shi, Kanagawa, Japan
Kosugi Dermatology Clinic
🇯🇵
Kawasaki-shi, Kanagawa, Japan
NTT Medical Center Tokyo
🇯🇵
Shinagawa-ku, Tokyo, Japan
Ajou University Hospital
🇰🇷
Suwon-si, Gyeonggi-do, Korea, Republic of
Uniwersyteckie Centrum Kliniczne
🇵🇱
Gdansk, Poland
Hallym University Dongtan Sacred Heart Hospital
🇰🇷
Hwaseong-si, Gyeonggi-do, Korea, Republic of
SPZOZ Centralny Szpital Kliniczny
🇵🇱
Lodz, Poland
Hallym University Kangnam Sacred Heart Hospital
🇰🇷
Seoul, Korea, Republic of
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
🇵🇱
Lublin, Poland
Klinika Osipowicz and Turkowski Spzoo Opieka Wielospecjalistyczna Osipowicz and Turkowski
🇵🇱
Warszawa, Poland
Hospital del Mar
🇪🇸
Barcelona, Cataluña, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸
Barcelona, Cataluña, Spain
Hospital Universitari de Bellvitge
🇪🇸
Hospitalet de LLobregat, Cataluña, Spain
Hospital Arnau de Vilanova de Valencia
🇪🇸
Valencia, Comunidad Valenciana, Spain
Hospital General Universitario de Valencia
🇪🇸
Valencia, Comunidad Valenciana, Spain
Henry Ford Medical Center - New Center One
🇺🇸
Detroit, Michigan, United States
Severance Hospital, Yonsei University Health System
🇰🇷
Seoul, Korea, Republic of