A Phase 2b Study of CSL112 in Subjects With Acute Myocardial Infarction.
- Conditions
- Acute Myocardial Infarction
- Interventions
- Biological: CSL112Biological: Placebo
- Registration Number
- NCT02108262
- Lead Sponsor
- CSL Behring
- Brief Summary
This is a multicenter randomized, double-blind, placebo-controlled, parallel-group, dose-ranging phase 2b study to investigate the hepatic and renal safety and tolerability of multiple dose administration of two dose levels of CSL112 compared with placebo in subjects with acute myocardial infarction (AMI).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1267
- Men or women, at least 18 years of age, with evidence of myocardial necrosis in a clinical setting consistent with a type I (spontaneous) acute myocardial infarction (AMI), in the last week.
- Ongoing hemodynamic instability
- Evidence of hepatobiliary disease
- Evidence of chronic kidney disease (CKD) (Stage III, IV, or V), defined as moderate or severe renal impairment or if subject is receiving dialysis
- Evidence of unstable renal function
- History of acute kidney injury after previous exposure to an intravenous contrast agent.
- Known history of allergies, hypersensitivity or deficiencies to CSL112 or any of its components
- Other severe comorbid condition, concurrent medication, or other issue that renders the subject unsuitable for participation in the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CSL112 - low dose CSL112 CSL112 (low dose) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112 - high dose CSL112 CSL112 (high dose) is to be administered as an IV infusion once weekly for 4 consecutive weeks. Placebo Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion.
- Primary Outcome Measures
Name Time Method Percent of Participants With Clinically Important Change in Renal Status From baseline (before first infusion) to Day 29. A clinically important change in renal status is defined as a serum creatinine (Cr) increase to ≥ 1.5 x the baseline value that is confirmed upon repeat measurement.
Percent of Participants With Clinically Important Change in Drug-induced Liver Injury From baseline (before first infusion) to Day 29. A clinically important change in drug-induced liver injury is defined as a change (from baseline) in alanine aminotransferase (ALT) greater than 3 times the upper limit of normal (ULN) or a change in total bilirubin greater than 2 times ULN, that is confirmed upon repeat measurement.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants Before and for 7 days after the first infusion Tmax is time to maximal plasma concentration
Change From Baseline in Serum Antibodies to CSL112 and apoA-I Before first infusion, up to approximately Day 112 The Percentage of Participants With a Time-to-first Major Adverse Cardiovascular Event (MACE) From the start of the first infusion up to approximately 382 days The MACE is a 4-component composite comprised of the time to the first of the following events: CV death, nonfatal myocardial infarction, ischemic stroke (non-hemorrhagic), and hospitalization for unstable angina.
Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants Before first infusion and end of first infusion Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) are analytes of CSL112
Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function Before and for 7 days after the first infusion Tmax is time to maximal plasma concentration
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants Before first infusion and end of fourth infusion Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after first infusion Cmax is the maximal plasma concentration.
Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after first infusion Cmax is the maximal plasma concentration.
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants Before and for 7 days after the fourth infusion Tmax is time to maximal plasma concentration
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function Before and for 7 days after the fourth infusion Tmax is time to maximal plasma concentration
Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment Before and for 7 days after the first infusion Tmax is time to maximal plasma concentration
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment Before and for 7 days after the fourth infusion Tmax is time to maximal plasma concentration
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after first infusion Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function Before first infusion and end of first infusion apoA-I and PC are analytes of CSL112
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function Before first infusion and end of fourth infusion apoA-I and PC are analytes of CSL112
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment Before first infusion and end of fourth infusion apoA-I and PC are analytes of CSL112
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Cmax is the maximal plasma concentration.
Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after first infusion Cmax is the maximal plasma concentration.
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Cmax is the maximal plasma concentration.
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after first infusion Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after first infusion AUC from baseline to time point t (AUC0-t)
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after fourth infusion AUC from baseline to time point t (AUC0-t)
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after first infusion AUC0-∞ is plasma area under the curve (AUC0-infinity)
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment Before first infusion and end of first infusion apoA-I and PC are analytes of CSL112
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Cmax is the maximal plasma concentration.
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after fourth infusion AUC0-∞ is plasma area under the curve (AUC0-infinity)
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after first infusion Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after first infusion Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after first infusion Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after first infusion Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after fourth infusion AUC from baseline to time point t (AUC0-t)
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after first infusion AUC from baseline to time point t (AUC0-t)
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after fourth infusion AUC from baseline to time point t (AUC0-t)
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after fourth infusion AUC0-∞ is plasma area under the curve (AUC0-infinity)
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after first infusion Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after first infusion Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after first infusion Percent of Participants Who Experience Bleeding Events From the start of first infusion, up to approximately Day 112 The number of subjects who experience bleeding events as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al, 2011)
Number of Participants With Parvovirus B19 DNA in Serum Study Day 112 Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after first infusion AUC from baseline to time point t (AUC0-t)
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after first infusion AUC0-∞ is plasma area under the curve (AUC0-infinity)
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after fourth infusion AUC0-∞ is plasma area under the curve (AUC0-infinity)
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after first infusion AUC0-∞ is plasma area under the curve (AUC0-infinity)
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Change From Baseline in Plasma Volume of Distribution at Steady State (Vss) for apoA-I and PC After First Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after first infusion Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for All Participants Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Normal Renal Function Before first infusion (baseline) and for up to approximately 7 days after first infusion Percent of Participants With Any Adverse Event (AE) From the start of first infusion, up to approximately Day 382 Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19 Study Day 112 Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after first infusion Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment Before first infusion (baseline) and for up to approximately 7 days after fourth infusion Percent of Participants With the Occurrence of Suspected Adverse Drug Reactions From the start of first infusion, up to approximately Day 382 The overall percentage of subjects:
* with adverse events (AEs), including local tolerability events, that begin during or within 1 hour of an infusion; or
* with AEs considered to be causally related to the test product; or
* who experience an AE for which the incidence rate in an active treatment arm exceeds the exposure-adjusted incidence rate in the placebo arm by 30% or more, provided the difference in incidence rates is 1% or more.
Trial Locations
- Locations (189)
Study Site 12021
🇧🇬Haskovo, Bulgaria
Study Site 12013
🇧🇬Sofia, Bulgaria
Study Site - 13007
🇨🇦Quebec, Canada
Study Site 14006
🇨🇿Brno, Czechia
Study Site - 25003
🇫🇷Pessac, Gironde, France
Study Site 17005
🇩🇪Berlin, Berin, Germany
Study Site 17009
🇩🇪Berlin, Germany
Study Site 17002
🇩🇪Berlin, Germany
Study Site - 23001
🇪🇸Barcelona, Spain
Study Site - 23003
🇪🇸Madrid, Spain
Study Site - 23013
🇪🇸Madrid, Spain
Study Site - 23011
🇪🇸Valencia, Spain
Study Site - 16168
🇺🇸Concord, California, United States
Study Site 16078
🇺🇸Huntsville, Alabama, United States
Study Site - 24006
🇬🇧Clydebank, Dunbartonshire, United Kingdom
Study Site - 23007
🇪🇸Malaga, Spain
Study Site - 23006
🇪🇸Santiago de Compostela, La Coruna, Spain
Study Site - 24010
🇬🇧Leicester, Leicestershire, United Kingdom
Study Site - 23005
🇪🇸Barcelona, Spain
Study Site - 23009
🇪🇸Tarragona, Spain
Study Site - 24009
🇬🇧Newcastle upon Tyne, Tyne & Wear, United Kingdom
Study Site - 23004
🇪🇸Madrid, Spain
Study Site - 23002
🇪🇸Barcelona, Spain
Study Site - 24003
🇬🇧London, Greater London, United Kingdom
Study Site 16047
🇺🇸Cincinnati, Ohio, United States
Study Site 16003
🇺🇸Jacksonville, Florida, United States
Study Site 16112
🇺🇸Boise, Idaho, United States
Study Site 24005
🇬🇧Romford, Essex, United Kingdom
Study Site - 24004
🇬🇧Basildon, Essex, United Kingdom
Study Site 16060
🇺🇸Evanston, Illinois, United States
Study Site 16102
🇺🇸Indianapolis, Indiana, United States
Study Site 16179
🇺🇸Elkhart, Indiana, United States
Study Site 16168
🇺🇸Concord, California, United States
Study Site 16022
🇺🇸Torrance, California, United States
Study Site 16135
🇺🇸Danbury, Connecticut, United States
Study Site 16170
🇺🇸Bridgeport, Connecticut, United States
Study Site 16144
🇺🇸Atlanta, Georgia, United States
Study Site 16130
🇺🇸Littleton, Colorado, United States
Study Site 16148
🇺🇸Clearwater, Florida, United States
Study Site 16025
🇺🇸West Des Moines, Iowa, United States
Study Site 16004
🇺🇸Lexington, Kentucky, United States
Study Site 16088
🇺🇸Lexington, Kentucky, United States
Study Site 16208
🇺🇸Alexandria, Louisiana, United States
Study Site 16062
🇺🇸Auburn, Maine, United States
Study Site 16031
🇺🇸Baltimore, Maryland, United States
Study Site 16079
🇺🇸Bangor, Maine, United States
Study Site 16061
🇺🇸Petoskey, Michigan, United States
Study Site 16234
🇺🇸Saint Paul, Minnesota, United States
Study Site 16033
🇺🇸Brooklyn, New York, United States
Study Site 16063
🇺🇸Tupelo, Mississippi, United States
Study Site 16174
🇺🇸Buffalo, New York, United States
Study Site 16213
🇺🇸New York, New York, United States
Study Site 16201
🇺🇸Elizabeth City, North Carolina, United States
Study Site 16017
🇺🇸Philadelphia, Pennsylvania, United States
Study Site 16026
🇺🇸Hershey, Pennsylvania, United States
Study Site 16014
🇺🇸High Point, North Carolina, United States
Study Site 16100
🇺🇸Lancaster, Pennsylvania, United States
Study Site 16015
🇺🇸Amarillo, Texas, United States
Study Site 16039
🇺🇸Greenwood, South Carolina, United States
Study Site 16202
🇺🇸Greeneville, Tennessee, United States
Study Site 16018
🇺🇸Rapid City, South Dakota, United States
Study Site 16099
🇺🇸Dallas, Texas, United States
Study Site 16241
🇺🇸Wichita Falls, Texas, United States
Study Site 10005
🇦🇺Adelaide, South Australia, Australia
Study Site 16166
🇺🇸Wausau, Wisconsin, United States
Study Site 10002
🇦🇺Herston, Queensland, Australia
Study Site 10012
🇦🇺Woodville South, South Australia, Australia
Study Site 10006
🇦🇺Epping, Victoria, Australia
Study Site 11001
🇦🇹Wien, Austria
Study Site 12006
🇧🇬Dobrich, Bulgaria
Study Site 12019
🇧🇬Pazardzhik, Bulgaria
Study Site 12017
🇧🇬Sandanski, Bulgaria
Study Site 12010
🇧🇬Sofia, Bulgaria
Study Site 12011
🇧🇬Varna, Bulgaria
Study Site 12007
🇧🇬Yambol, Bulgaria
Study Site 12002
🇧🇬Veliko Tarnovo, Bulgaria
Study Site - 13003
🇨🇦Edmonton, Alberta, Canada
Study Site - 13002
🇨🇦Edmonton, Alberta, Canada
Study Site - 13017
🇨🇦Penticton, British Columbia, Canada
Study Site - 13019
🇨🇦St. Johns, Newfoundland and Labrador, Canada
Study Site - 13008
🇨🇦London, Ontario, Canada
Study Site - 13014
🇨🇦Montreal, Quebec, Canada
Study Site - 13010
🇨🇦Newmarket, Ontario, Canada
Study Site 14010
🇨🇿Brno, Czechia
Study Site 14004
🇨🇿Hradec Kralove, Czechia
Study Site 14012
🇨🇿Jablonec nad Nisou, Czechia
Study Site 14011
🇨🇿Jihlava, Czechia
Study Site 14017
🇨🇿Nachod, Czechia
Study Site 14016
🇨🇿Kolin, Czechia
Study Site 14007
🇨🇿Ostrava, Czechia
Study Site 14003
🇨🇿Pardubice, Czechia
Study Site 14002
🇨🇿Praha 10, Czechia
Study Site 14001
🇨🇿Praha 2, Czechia
Study Site 14015
🇨🇿Praha 2, Czechia
Study Site 14008
🇨🇿Praha 4 - Krc, Czechia
Study Site 14005
🇨🇿Usti nad Orlici, Czechia
Study Site 14009
🇨🇿Praha 5, Czechia
Study Site 14014
🇨🇿Teplice, Czechia
Study Site - 25004
🇫🇷Pau, Pyrenees Atlantiques, France
Study Site - 25005
🇫🇷Toulouse cedex 3, Haute Garonne, France
Study Site - 25008
🇫🇷Nantes cedex, Loire Antlantique, France
Study Site - 25002
🇫🇷Paris cedex 12, Paris, France
Study Site 17001
🇩🇪Freiburg, Baden Wuerttemberg, Germany
Study Site - 25001
🇫🇷Paris, France
Study Site 17012
🇩🇪Hannover, Niedersachsen, Germany
Study Site 17014
🇩🇪Franfurt, Hessen, Germany
Study Site 17007
🇩🇪Luedenscheid, Nordrhein Westfalen, Germany
Study Site 17010
🇩🇪Ludwigshafen, Rheinland Pfalz, Germany
Study Site 17011
🇩🇪Mainz, Rheinland Pfalz, Germany
Study Site 17003
🇩🇪Berlin, Germany
Study Site 17006
🇩🇪Hamburg, Germany
Study Site 18002
🇭🇺Gyor, Hungary
Study Site 18008
🇭🇺Budapest, Hungary
Study Site 18003
🇭🇺Pecs, Hungary
Study Site 19010
🇮🇱Ashkelon, Israel
Study Site 19003
🇮🇱Jerusalem, Israel
Study Site 19007
🇮🇱Jerusalem, Israel
Study Site 19005
🇮🇱Haifa, Israel
Study Site 19006
🇮🇱Beer Sheva, Israel
Study Site 19004
🇮🇱Holon, Israel
Study Site 20011
🇮🇹Napoli, Italy
Study Site 20003
🇮🇹Legnano, Milano, Italy
Study Site 19002
🇮🇱Nahariya, Israel
Study Site 19008
🇮🇱Safed, Israel
Study Site 20002
🇮🇹Magenta, Milano, Italy
Study Site 20008
🇮🇹Rozzano, Milano, Italy
Study Site 20009
🇮🇹Benevento, Italy
Study Site 20001
🇮🇹Terni, Italy
Study Site 20012
🇮🇹Roma, Italy
Study Site 20006
🇮🇹Udine, Italy
Study Site 21001
🇳🇱Alkmaar, Netherlands
Study Site 21006
🇳🇱Amsterdam, Netherlands
Study Site 21013
🇳🇱Amsterdam, Netherlands
Study Site 21004
🇳🇱Ede, Netherlands
Study Site 21016
🇳🇱Amsterdam, Netherlands
Study Site 21014
🇳🇱Leeuwarden, Netherlands
Study Site 21003
🇳🇱Nieuwegein, Netherlands
Study Site 21008
🇳🇱Nijmegen, Netherlands
Study Site 21009
🇳🇱Rotterdam, Netherlands
Study Site 21010
🇳🇱Sneek, Netherlands
Study Site 21011
🇳🇱Venlo, Netherlands
Study Site 21015
🇳🇱Tilburg, Netherlands
Study Site 22009
🇵🇱Kielce, Poland
Study Site - 22014
🇵🇱Lodz, Poland
Study Site - 23010
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Study Site - 23012
🇪🇸A Coruna, La Coruna, Spain
Study Site 15001
🇩🇰Alborg, Denmark
Study Site 15005
🇩🇰Esbjerg, Denmark
Study Site 15002
🇩🇰Hellerup, Denmark
Study Site 15004
🇩🇰Hvidovre, Denmark
Study Site 15003
🇩🇰Odense, Denmark
Study Site 16101
🇺🇸Birmingham, Alabama, United States
Study Site 16028
🇺🇸Detroit, Michigan, United States
Study Site 16056
🇺🇸Durham, North Carolina, United States
Study Site 20007
🇮🇹Rimini, Italy
Study Site - 22005
🇵🇱Wroclaw, Poland
Study Site 18001
🇭🇺Budapest, Hungary
Study Site 12005
🇧🇬Blagoevgrad, Bulgaria
Study Site 12008
🇧🇬Burgas, Bulgaria
Study Site 12014
🇧🇬Plovdiv, Bulgaria
Study Site 12001
🇧🇬Sofia, Bulgaria
Study Site 12009
🇧🇬Pazardzhik, Bulgaria
Study Site 12018
🇧🇬Plovdiv, Bulgaria
Study Site 18007
🇭🇺Nyiregyhaza, Hungary
Study Site 11002
🇦🇹Vienna, Austria
Study Site 12016
🇧🇬Pleven, Bulgaria
Study Site 12003
🇧🇬Sofia, Bulgaria
Study Site 12004
🇧🇬Sofia, Bulgaria
Study Site 12012
🇧🇬Sofia, Bulgaria
Study Site - 22010
🇵🇱Grodzisk Mazowiecki, Poland
Study Site 18005
🇭🇺Budapest, Hungary
Study Site - 13012
🇨🇦Victoria, British Columbia, Canada
Study Site 11004
🇦🇹Innsbruck, Austria
Study Site - 22016
🇵🇱Wejherowo, Poland
Study Site - 22012
🇵🇱Inowroclaw, Poland
Study Site 10007
🇦🇺Geelong, Victoria, Australia
Study Site 18009
🇭🇺Szeged, Hungary
Study Site 18006
🇭🇺Szolnok, Hungary
Study Site - 22015
🇵🇱Gdansk, Poland
Study Site - 22006
🇵🇱Walbrzych, Poland
Study Site - 22007
🇵🇱Krakow, Poland
Study Site - 22013
🇵🇱Starogard Gdanski, Poland
Study Site - 22008
🇵🇱Warszawa, Poland
Study Site 19009
🇮🇱Ramat Gan, Israel
Study Site 16211
🇺🇸Minneapolis, Minnesota, United States
Study Site 16016
🇺🇸Louisville, Kentucky, United States
Study Site 16147
🇺🇸Sacramento, California, United States
Study Site 16024
🇺🇸Winston-Salem, North Carolina, United States
Study Site 16038
🇺🇸Richmond, Virginia, United States