Long-Term Tolerability and Safety of HYQVIA/HyQvia in CIDP

Phase 3

Completed

Conditions: Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Interventions: Biological: HYQVIA

Registration Number: NCT02955355

Lead Sponsor: Baxalta now part of Shire

Brief Summary: Adults with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) who have completed study 161403 will be able to take part in this study.

The main aim of the study is to evaluate side effects in the long-term treatment with HYQVIA/HyQvia.

All participants will receive HYQVIA/HyQvia in the same way as they were receiving in study 161403. The dosing interval of HYQVIA/HyQvia can be adjusted after 12 weeks of treatment in study 161505 if the study doctor determines that it is safe to do so.

Participants will visit the clinic within 1 week after the first and second dose of HYQVIA/HyQvia and then every 12 weeks for the duration of the study.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 85

Inclusion Criteria

Has completed Epoch 1 of Study 161403 without CIDP worsening.
If female of childbearing potential, the participant must have a negative pregnancy test at baseline and agree to employ adequate birth control measures (eg, birth control pills/patches, intrauterine device, or diaphragm or condom [for male partner] with spermicidal jelly or foam) throughout the course of the study.

Exclusion Criteria

Participant has a serious medical condition such that the participant's safety or medical care would be impacted by participation in this Extension Study.
New medical condition that developed during participation in study 161403 that, in the judgment of the investigator, could increase risk to the participant or interfere with the evaluation of investigational medicinal product (IMP) and/or conduct of the study.
Participant is scheduled to participate in another non-Baxalta clinical study involving an IP or investigational device during the course of this study.
The participant is nursing or intends to begin nursing during the course of the study
Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study (with the exception of study 161403) involving an IP or investigational device during the course of this study.
The participant is a family member or employee of the investigator.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HYQVIA/HyQvia	HYQVIA	Participants received HYQVIA/HyQvia (recombinant human hyaluronidase \[rHuPH20\] at a dose of 80 units per gram (U/g) immunoglobulin G \[IgG\], followed by subcutaneous \[SC\] immune globulin infusion \[IGI\] 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment-Emergent Adverse Events That May be a Result of Immune-Mediated Responses	From the first dose of study drug up to end of study (up to 6.6 years)	Percentage of participants with TEAEs that may be a result of immune-mediated response to either immunoglobulin, rHuPH20, or other factors such as allergic reactions, immune complex-mediated reactions: local, complex-mediated reactions: systemic, thrombotic and embolic events were assessed. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. The percentage was rounded off to the nearest decimal.
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Participant	From the first dose of study drug up to end of study (up to 6.6 years)	TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". An adverse event that was "possibly related" or "probably related" to IP, or for which the relationship was unknown or missing, was considered as a "related AE". Data for number of events per participant was assessed at the group level calculated by dividing number of events by total number of participants in the Safety Analysis Set.
Number of Participants With Adverse Reactions (ARs) or Suspected Adverse Reactions (SARs) Categorized as Serious and Non-serious	From the first dose of study drug up to end of study (up to 6.6 years)	An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Serious AR/SAR=any AR/SAR that is an untoward medical occurrence which at any dose meets one or more of following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of existing hospitalization, results in persistent or significant disability/incapacity,is a congenital anomaly/birth defect,is a medically important event,thromboembolic events,hemolytic anemia. Nonserious AR/SAR=AR/SAR that does not meet the criteria.
Number of Infusions Associated With One or More Local TEAEs	From the first dose of study drug up to end of study (up to 6.6 years)	An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Infusions associated with one or more AEs are defined as follows: if an AE occurs after an infusion but prior to the next infusion that infusion is associated with that AE.
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Infusion	From the first dose of study drug up to end of study (up to 6.6 years)	TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per infusion was assessed at the group level calculated by dividing number of events by total number of infusions administered to participants in the Safety Analysis Set.
Number of Serious and Non-Serious ARs or SARs Associated With Infusions	From the first dose of study drug up to end of study (up to 6.6 years)	An AR/SAR=any AE that meets any of following criteria: AE considered by either investigator and/or sponsor to be possibly or probably related to IP administration, begins during infusion of IP or within 72 hours following end of IP infusion,or AE for which causality assessment is missing or indeterminate. ARs/SARs associated with an infusion=AEs considered by the investigator to be occurring after administration of IP. Serious AR/SAR=any AR/SAR that is an untoward medical occurrence which at any dose meets one or more of following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of existing hospitalization, results in persistent or significant disability/incapacity,is a congenital anomaly/birth defect,is a medically important event,thromboembolic events,hemolytic anemia. Nonserious AR/SAR=AR/SAR that does not meet the criteria. Participants can have more than one AR/SAR associated with infusion.
Number of Participants Who Had >1:10,000 Anti-rHuPH20 Binding Antibody Titers With Neutralizing Antibodies	From the first dose of study drug up to end of study (up to 6.6 years)
Number of Participants With Any Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs), Regardless of Causality	From the first dose of study drug up to end of study (up to 6.6 years)	An AE was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Treatment emergent adverse events (TEAEs) were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study.
Number of Participants With Causally Related Treatment-emergent SAEs and AEs	From the first dose of study drug up to end of study (up to 6.6 years)	An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Causality was used to determine whether there was a reasonable possibility that the IP was etiologically related to/associated with the AE.
Number of Treatment-Emergent SAEs and AEs Associated With Infusions, Regardless of Causality	From the first dose of study drug up to end of study (up to 6.6 years)	An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. AEs associated with an infusion are defined as AEs occurring after administration of IP (or any TEAE). Participants can have more than one TEAE associated with infusion.
Number of Causally Related Treatment-Emergent SAEs and AEs Associated With Infusions	From the first dose of study drug up to end of study (up to 6.6 years)	An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. AEs associated with an infusion are defined as AEs occurring after administration of IP (or any TEAE). Causality was used to determine whether there was a reasonable possibility that the IP was etiologically related to/associated with the AE.
Number of TEAEs Temporally Associated With Infusions	From the first dose of study drug up to end of study (up to 6.6 years)	TEAEs that occurred during infusion or within 72 hours post-infusion were considered to be temporally associated with infusions. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Participants can have more than one TEAE temporally associated with infusion.
Number of Infusions Associated With One or More Systemic TEAEs	From the first dose of study drug up to end of study (up to 6.6 years)	An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the Medical Dictionary for Regulatory Activities (MedDRA) Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Infusions associated with one or more AEs are defined as follows: if an AE occurs after an infusion but prior to the next infusion that infusion is associated with that AE.
Number of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Intolerability and/or TEAEs	From the first dose of study drug up to end of study (up to 6.6 years)	An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study.
Rate of Moderate or Severe TEAEs That May be a Result of Immune-Mediated Responses, Expressed as Number of Events Per 100 Infusions	From the first dose of study drug up to end of study (up to 6.6 years)	An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. A moderate or severe AE could be a result of immune-mediated response to either immunoglobulin, rHuPH20, or other concomitant medications. The severity of each AE was assessed by the investigator using clinical expertise. Data for number of events per 100 infusions was assessed at the group level calculated by dividing number of events by total number of infusions and multiplying that by 100.
Number of Participants With Treatment-Emergent Local Tolerability Events During Ramp-up	During the ramp-up (8 weeks)	Participants with local tolerability events were those for which the infusion rate was reduced and/or the infusion was interrupted or stopped due to intolerability and/or AEs. These events were assessed during the initial ramp-up for each participant i.e., during the first 8 weeks of open-label extension study 161505 \[NCT02955355\] among participants originally randomized to placebo (as being in the placebo arm, they had no ramp-up during the 161403 \[NCT02549170\] study) versus during the 8-week ramp-up for participants originally randomized to active HYQVIA in double-blind 161403 study. Thus, the data for this outcome measure are presented per the bifurcation of participants in the study 161403.
Number of Participants With Local Infusion Reactions, as a Function of Dosing Interval, Infusion Rate Per Site, and Infusion Volume Per Site	From the first dose of study drug up to end of study (up to 6.6 years)	Local infusion reactions were defined as local (administration site-related) adverse events. Median infusion rate per site was derived as the median value across all participants, per participant's average infusion rate, by site: actual volume infused / duration in hours of infusion / number of sites. Median infusion volume per site was derived as the median value across all participants, per participant's average actual volume infused, by site: actual volume infused / number of sites. Number of participants with local infusion reactions as a function of each of the categories are presented below.
Number of Participants Whose Anti-Hyaluronidase Binding Antibody Titers Rose by ≥4-fold From Baseline	Baseline, up to 6.6 years	Number of participants whose anti-hyaluronidase antibody titers rose by ≥4 fold from the baseline value at any point during the study was assessed.
Number of Participants With Binding Antibodies to rHuPH20	From the first dose of study drug up to end of study (up to 6.6 years)	Binding antibodies were defined as anti-rHuPH20 titer ≥1:160.
Number of Participants With a Decline of Anti-rHuPH20 Binding Antibody Titers to the Antibody Titer Level at Baseline in Study 161403 or to <1:160 Antibody Titer Level at the Study Completion or Early Discontinuation	From the first dose of study drug up to end of study (up to 6.6 years)
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Participant	From the first dose of study drug up to end of study (up to 6.6 years)	TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per participant was assessed at the group level calculated by dividing number of events by total number of participants in the Safety Analysis Set.
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year	From the first dose of study drug up to end of study (up to 6.6 years)	TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Events per participant-years was calculated as follows: 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the Safety Analysis Set, divided by 365.25).
Number of Participants With a TEAE That Led to Discontinuation From Study	From the first dose of study drug up to end of study (up to 6.6 years)	An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study.
Number of Participants With Neutralizing Antibodies Binding to rHuPH20	From the first dose of study drug up to end of study (up to 6.6 years)
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Infusion	From the first dose of study drug up to end of study (up to 6.6 years)	TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". An adverse event that was "possibly related" or "probably related" to IP, or for which the relationship was unknown or missing, was considered as a "related AE". Data for number of events per infusion was assessed at the group level calculated by dividing number of events by total number of infusions administered to participants in the Safety Analysis Set.
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per 1000 Participant-year	From the first dose of study drug up to end of study (up to 6.6 years)	TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". An adverse event that was "possibly related" or "probably related" to IP, or for which the relationship was unknown or missing, was considered as a "related AE". Events per participant-years was calculated as follows: 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the Safety Analysis Set, divided by 365.25).
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per 1000 Participant-year	From the first dose of study drug up to end of study (up to 6.6 years)	An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Systemic AEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local AEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Events per participant-years was calculated as follows: 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the Safety Analysis Set, divided by 365.25).
Number of Participants With Moderate or Severe TEAEs That May be a Result of Immune-Mediated Responses	From the first dose of study drug up to end of study (up to 6.6 years)	An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. A moderate or severe AE could be a result of immune-mediated response to either immunoglobulin, rHuPH20, or other factors such as allergic reactions, immune complex-mediated reactions: local, complex-mediated reactions: systemic, thrombotic and embolic events. The severity of each AE was assessed by the investigator using clinical expertise based on the following description: moderate=AE produces limited impairment of function and may require therapeutic intervention and produces no sequela/sequelae; severe=AE results in a marked impairment of function and may lead to temporary inability to resume usual life pattern and produces sequela/sequelae, which require (prolonged) therapeutic intervention.
Number of Participants That Experienced Treatment-Emergent Local Infusion Site Reactions	From the first dose of study drug up to end of study (up to 6.6 years)	TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. AE=any untoward medical occurrence in participant administered an IP that does not have causal relationship with treatment. Adverse reaction/suspected adverse reaction=AE that is considered by the investigator to be possibly or probably related to IP administration, or for which the causality is indeterminate or missing, or that begins during infusion of IP or within 72 hours following the end of IP infusion. All local infusion site treatment-emergent AEs were reported as adverse reactions.
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Infusion	From the first dose of study drug up to end of study (up to 6.6 years)	An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Systemic AEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local AEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per infusion was assessed at the group level calculated by dividing number of events by total number of infusions administered to participants in the Safety Analysis Set.
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Participant	From the first dose of study drug up to end of study (up to 6.6 years)	An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Systemic AEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local AEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per participant was assessed at the group level calculated by dividing number of events by total number of participants in the Safety Analysis Set.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Had >1:10,000 Anti-rHuPH20 Binding Antibody Titers Showing Cross Reactivity With Hyaluronidase (Hyal)-1,2 and 4	From the first dose of study drug up to end of study (up to 6.6 years)

Trial Locations

Locations (35): Fondazione Istituto Neurologico Casimiro Mondino
🇮🇹
Pavia, Italy
Arizona Neuromuscular Research Center
🇺🇸
Phoenix, Arizona, United States
Fakultna nemocnica Nitra
🇸🇰
Nitra, Slovakia
Århus Universitetshospital
🇩🇰
Aarhus C, Denmark
Uniwersyteckie Centrum Kliniczne
🇵🇱
Gdansk, Poland
Instituto de Neurologia de Curitiba - Hospital Ecoville
🇧🇷
Curitiba, Paraná, Brazil
University of Alberta Hospital
🇨🇦
Edmonton, Alberta, Canada
Hosp.Britanico de Buenos Aires
🇦🇷
Ciudad Autonoma Buenos Aires, Argentina
Toronto General Hospital, University Health Network
🇨🇦
Toronto, Ontario, Canada
Institucion Prestadora de Servicios de Salud de la Universidad de Antioquia "IPS UNIVERSITARIA"
🇨🇴
Medellin, Colombia
Fakultni nemocnice Ostrava
🇨🇿
Ostrava, Poruba, Czechia
Fakultni nemocnice v Motole
🇨🇿
Prague 5, Czechia
CHU de Nice
🇫🇷
Nice, Alpes Maritimes, France
Groupe Hospitalier Pellegrin - Hôpital Pellegrin
🇫🇷
Bordeaux Cedex, Gironde, France
University Hospital of Patra
🇬🇷
Patras, Greece
Hopital Neurologique Pierre Wertheimer
🇫🇷
Bron Cedex, Rhone, France
Universitaetsklinikum Leipzig AoeR
🇩🇪
Leipzig, Sachsen, Germany
Azienda Ospedaliero Universitaria San Martino
🇮🇹
Genova, Italy
Celal Bayar University Medical Faculty
🇹🇷
Manisa, Turkey
Azienda Ospedaliera Universitaria Policlinico G. Martino
🇮🇹
Messina, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹
Pisa, Italy
Azienda Ospedaliero-Universitaria Santa Maria della Misericordia
🇮🇹
Udine, Italy
Instituto Nacional de Ciencias Médicas y Nutricion Dr. Salvador Zubiran
🇲🇽
Mexico, Distrito Federal, Mexico
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
🇵🇱
Lublin, Poland
Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego
🇵🇱
Łódź, Poland
Clinical Center of Serbia
🇷🇸
Belgrade, Serbia
Military Medical Academy
🇷🇸
Belgrade, Serbia
Clinical Center Nis
🇷🇸
Nis, Serbia
LHSC - University Hospital
🇨🇦
London, Ontario, Canada
Dokuz Eylul University Faculty of Medicine
🇹🇷
Izmir, Turkey
Pamukkale Uni. Med. Fac.
🇹🇷
Denizli, Turkey
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Selcuk Universitesi Selcuklu Tip Fakultesi Hastanesi
🇹🇷
Konya, Turkey
King's College Hospital
🇬🇧
London, Greater London, United Kingdom
The Walton Centre
🇬🇧
Liverpool, Merseyside, United Kingdom