A Medical Research Study Designed to Determine if Venglustat Can be a Future Treatment for ADPKD Patients
- Conditions
- Polycystic Kidney, Autosomal Dominant
- Interventions
- Drug: Placebo
- Registration Number
- NCT03523728
- Lead Sponsor
- Genzyme, a Sanofi Company
- Brief Summary
Primary Objective:
To determine the effect of venglustat on the rate of total kidney volume (TKV) growth (Stage 1) and estimated glomerular filtration rate (eGFR) decline in participants at risk of rapidly progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD) (Stage 2).
Secondary Objectives:
* To determine the effect of venglustat on the rate of renal function decline (Stage 1) and on the rate of TKV growth (Stage 2).
* To evaluate the pharmacokinetics (PK) of venglustat in ADPKD participants (Stages 1 and 2).
* To determine the effect of venglustat on pain and fatigue, based on participant reported diary (Stages 1 and 2).
* Safety/tolerability objectives:
* To characterize the safety profile of venglustat (Stages 1 and 2).
* To evaluate the effect of venglustat on mood using Beck Depression Inventory II (BDI-II) (Stages 1 and 2).
* To evaluate the effect of venglustat on the lens by ophthalmological examination (Stages 1 and 2).
- Detailed Description
Study duration per participant was 26 months (maximal) that included a screening period of 15 days, run-in period of 2 weeks, a 24-month treatment period, and a follow-up 30 days after final dose of investigational medicinal product (IMP).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 478
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Stage 1- Venglustat 8 mg Venglustat Participants from Stage 1 were randomized to receive venglustat 8 milligrams (mg) (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months. Stage 1- Venglustat 15 mg Placebo Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Stage 2- Placebo Placebo Participants from Stage 2 were randomized to receive 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Stage 1- Placebo Placebo Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months. Stage 2- Venglustat 15 mg Venglustat Participants from Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months. Stage 1- Venglustat 15 mg Venglustat Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months.
- Primary Outcome Measures
Name Time Method Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Stage 1 From Baseline to Month 18 Total kidney volume is a measure for assessing disease progression in participants with ADPKD, a prognostic biomarker of renal function decline and progression to end-stage renal disease. Kidney volume was assessed using magnetic resonance imaging (MRI). The annualized slope of change in TKV (in percentage \[%\] per year) in each treatment group was obtained from the back-transformation of the mean slope of log10-transformed TKV obtained from the linear mixed effect model. The model included fix effects of treatment (venglustat 15 mg, venglustat 8 mg or placebo), mayo imaging classification (as per randomization stratification factor: class 1C versus 1D versus 1E), time (as continuous variable in years), treatment \* time interaction and mayo imaging classification \* time interaction and included random intercept and slope.
Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) From Baseline to Month 24: Combined Stage 1 and Stage 2 From Baseline to Month 24 An eGFR was used to measure level of kidney function and determine the stage of kidney disease in ADPKD participants. Baseline eGFR was defined for each participant as the average of eGFR values assessed prior or equal to first dose of study drug or randomization for participants randomized and not exposed. Annualized rate of change in eGFR in each treatment group was obtained from the linear mixed effect model including the fixed categorical effects of treatment group (venglustat 15 mg, venglustat 8 mg or placebo), mayo imaging classification (as per interactive response technology \[IRT\]: 1C, 1D, 1E), time (as continuous variable in years), treatment-by-time, mayo imaging classification-by-time, and included random intercept and slope.
- Secondary Outcome Measures
Name Time Method Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Month 24: Stage 1 From Baseline to Month 24 An eGFR was used to measure level of kidney function and determine the stage of kidney disease in ADPKD participants. Baseline eGFR was defined for each participant as the average of eGFR values assessed prior or equal to first dose of study drug or randomization for participants randomized and not exposed. Annualized rate of change in eGFR was obtained from the linear mixed effect model including the fixed categorical effects of treatment group, mayo imaging classification (as per IRT), time (as continuous variable in years), treatment-by-time, mayo imaging classification-by-time, and included random intercept and slope. Due to early termination of study for futility, the two-steps analysis initially planned was not applicable, then the annualized rate of change from baseline in eGFR in Stage 1 population were assessed using all data available up to database lock (i.e., including Month 24 assessment). As this is a slope, it allowed to have more data and to reduce variability.
Change in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score From Baseline to Month 18: Stage 1 From Baseline to Month 18 The BPI-SF is a validated, self-administered questionnaire designed to measure a participant's perceived level of pain. The BPI-SF consisted of 15 items that use a numeric rating scale (NRS) to assess pain severity and pain interference in the past 24 hours and the past week. BPI-SF Item 3 asks participants to "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the past 24 hours." The NRS ranged from 0 (no pain) to 10 (worst imaginable pain), where higher scores indicates greater intensity of pain. Least-squares (LS) means, and standard errors (SE) were estimated from mixed-effect model with repeated measures (MMRM) analysis.
Change in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score From Baseline to Month 24: Combined Stage 1 and Stage 2 From Baseline to Month 24 The BPI-SF is a validated, self-administered questionnaire designed to measure a participant's perceived level of pain. The BPI-SF consisted of 15 items that use a NRS to assess pain severity and pain interference in the past 24 hours and the past week. BPI-SF Item 3 asks participants to "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the past 24 hours." The NRS ranged from 0 (no pain) to 10 (worst imaginable pain), where higher scores indicate greater intensity of pain. LS means and SE were estimated from MMRM analysis.
Change in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI-SF)-Item 3 Scale Score From Baseline to Month 24: Combined Stage 1 and Stage 2 From Baseline to Month 24 The BFI-SF is a 10-item, validated, self-administered questionnaire that was originally developed to assess fatigue severity. The 10-items were measured on a 0-10 scale, with 0 being 'does not interfere' and 10 being 'completely interferes.' BFI - Item 3 asks participants to "Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your worst level of fatigue during the past 24 hours. The NRS ranged from 0 (no fatigue) to 10 (worst imaginable fatigue). Higher global scores were associated with more severe fatigue. LS means and SE were estimated from MMRM analysis.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Stage 1 From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) was any untoward medical occurrence that at any dose: results in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed, worsened or became serious during the treatment-emergent (TE) period (defined as the time from the first investigational medicinal product \[IMP\] administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Combined Stage 1 and Stage 2 From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. SAE was any untoward medical occurrence that at any dose: results in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed, worsened or became serious during the TE period (defined as the time from the first IMP administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier).
Number of Participants With Potentially and Clinically Significant Abnormalities: Vital Signs: Combined Stage 1 and Stage 2 From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier Criteria for potentially clinically significant abnormalities: Sitting Systolic Blood Pressure: \<=95 millimeters of Mercury (mmHg) and decrease from Baseline \>=20 mmHg; \>=160 mmHg and increase from Baseline \>=20 mmHg; Sitting Diastolic Blood Pressure: \<=45 mmHg and decrease from Baseline \>=10 mmHg, \>=110 mmHg and increase from Baseline \>=10 mmHg; Sitting Heart Rate: \<=50 beats/minute and decrease from Baseline \>=20 beats/minute; \>=120 beats/minute and increase from Baseline \>=20 beats/minute; and Weight: \>=5% decrease from Baseline; \>=5% increase from Baseline.
Pharmacokinetics: Plasma Concentration of Venglustat: Stage 2 Month 1: Pre-dose and 3 hours Post-dose Venglustat plasma concentrations was determined using a validated LC-MS/MS method. Data for this outcome measure was not planned to be collected and analyzed for placebo arm.
Number of Participants With Potentially Clinically Significant Abnormalities: Hematology: Combined Stage 1 and Stage 2 From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier Criteria for potentially clinically significant abnormalities: Hemoglobin: less than or equal to (\<=) 115 grams per liter (g/L) \[Male\]; \<=95 g/L \[Female\]; greater than or equal to (\>=) 185 g/L \[Male\]; \>=165 g/L \[Female\]; Decrease from baseline \>=20 g/L; Hematocrit: \<=0.37 volume/volume (v/v) \[Male\]; \<=0.32 v/v \[Female\]; \>=0.55 v/v \[Male\]; \>=0.5 v/v \[Female\]; Erythrocyte (red blood cells \[RBC\]): \>=6\*10\^12 per liter (/L); Platelet: less than (\<) 100\*10\^9/L; \>=700\*10\^9/L; Leukocyte (white blood cells \[WBC\]): \<3\*10\^9/L \[Non-Black\]; \<2\*10\^9/L \[Black\], \>=16\*10\^9/L; Neutrophils: \<1.5\*10\^9/L \[Non-Black\]; \<1\*10\^9/L \[Black\]; Lymphocytes: greater than (\>) 4\*10\^9/L, Monocytes: \>0.7\*10\^9/L; Basophils: \>0.1\*10\^9/L; and Eosinophils: \>0.5\*10\^9/L or \>upper limit of normal (ULN) (if ULN \>=0.5\*10\^9/L).
Number of Participants With Potentially and Clinically Significant Abnormalities: Urinalysis: Combined Stage 1 and Stage 2 From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier Criteria for potentially clinically significant abnormalities: Urine pH: \<=4.6 and \>=8.
Number of Participants With Physical Examination Abnormalities: Combined Stage 1 and Stage 2 Baseline, Month 18, Month 24 Physical examination included: Head, Heart, Lung, Abdomen, Musculo/Skeletal, Skin, and Mental Status. Abnormality in physical examination was based on investigator's discretion. Results are based on the treatment emergent period which was defined as time from the first IMP administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier.
Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Combined Stage 1 and Stage 2 From Baseline to Month 18 Total kidney volume is a measure for assessing disease progression in participants with ADPKD, a prognostic biomarker of renal function decline and progression to end-stage renal disease. Kidney volume was assessed using MRI. The annualized slope of change in TKV (in % per year) in each treatment group was obtained from the back-transformation of the mean slope of log10-transformed TKV obtained from the linear mixed effect model. The model included fix effects of treatment (venglustat 15 mg, venglustat 8 mg or placebo), mayo imaging classification (as per randomization stratification factor: class 1C versus 1D versus 1E), time (as continuous variable in years), treatment \* time interaction and mayo imaging classification \* time interaction and included random intercept and slope.
Change in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI-SF)-Item 3 Scale Score From Baseline to Month 18: Stage 1 From Baseline to Month 18 The BFI-SF is a 10-item, validated, self-administered questionnaire that was originally developed to assess fatigue severity. The 10-items were measured on a 0-10 scale, with 0 being 'does not interfere' and 10 being 'completely interferes.' BFI - Item 3 asks participants to 'Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your worst level of fatigue during the past 24 hours. The NRS ranged from 0 (no fatigue) to 10 (worst imaginable fatigue). Higher global scores were associated with more severe fatigue. LS means and SE were estimated from MMRM analysis.
Pharmacokinetics: Plasma Concentration of Venglustat: Stage 1 Day 1: 3 hours Post-Dose, Month 1: Pre-Dose and 3 hours Post-Dose, Month 6: Pre-Dose, Month 18: Pre-Dose Venglustat plasma concentrations was determined using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Data for this outcome measure was not planned to be collected and analyzed for placebo arm.
Number of Participants With Potentially Clinically Significant Abnormalities: Clinical Chemistry: Combined Stage 1 and Stage 2 From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier Criteria for potentially clinically significant abnormalities: Glucose: \<=3.9 millimoles per liter (mmol/L) and \<lower limit of normal (LLN): \>=11.1 mmol/L (unfasted); \>=7 mmol/L (fasted); Albumin:\<=25 g/L; Sodium: \<=129 mmol/L; \>=160 mmol/L; Potassium: \<3 mmol/L; \>=5.5 mmol/L; Chloride: \<80 mmol/L, \>115 mmol/L; Creatinine: \>=150 micro millimoles per liter (mcmol/L) (Adults); \>=30% change from Baseline; \>=100% change from Baseline, Urea Nitrogen: \>=17 mmol/L; Alanine Aminotransferase (ALT): \>3 ULN; Aspartate Aminotransferase (AST): \>3 ULN; Alkaline Phosphatase: \>1.5 ULN; Total Bilirubin: \>1.5 ULN, \>2 ULN; ALT \>3 ULN and Bilirubin \>2 ULN; and Direct Bilirubin \>35% Bilirubin and Bilirubin \>1.5 ULN.
Number of Participants With Worsening Lens Opacity From Baseline During the Treatment-emergent Period: Combined Stage 1 and Stage 2 From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier Worsening of lens opacity classification system (LOCS) III score or World Health Organization (WHO) grade in nuclear opacification, cortical opacification and posterior subcapsular opacification were assessed for 'Any eye', 'Unilateral' and 'Bilateral' separately. A participant could be counted in all the 3 categories. In each category, the worst case was taken into account. To be evaluable for 'Any', a participant had to have at least one eye evaluable, whereas, for 'Unilateral' and 'Bilateral', a participant had to have both eyes evaluable. Therefore, the sum of 'Unilateral' + 'Bilateral' is not necessarily equal to 'Any' in the below table. The difference observed in 'Nuclear Opacification' in 15 mg group, comes from that 1 participant who had Unilateral worsening at a given visit and a Bilateral worsening at another visit. Therefore, this participant was counted as 'Unilateral', 'Bilateral' and counted only once in 'Any'. Results are based on the TE period.
Number of Participants With Potentially Clinically Significant Abnormalities: Electrocardiogram: Combined Stage 1 and Stage 2 From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier Criteria for potentially clinically significant abnormalities: Heart Rate: \<50 beats/minute; \<50 beats/minute and decrease from Baseline \>=20 beats/minute; \<40 beats/minute; \<40 beats/minute and decrease from Baseline \>=20 beats/min; \<30 beats/minute; \>90 beats/minute; \>90 beats/minute and increase from Baseline \>=20 beats/minute; \>100 beats/minute; \>100 beats/minute and increase from Baseline \>=20 beats/minute; \>120 beats/minute; \>120 beats/minute, increase from Baseline \>=20 beats/minute; PR Interval: \>200 milliseconds (msec); \>200 msec and increase from Baseline \>=25%; \>220 msec, \>240 msec; QRS Interval: \>110 msec; \>110 msec and increase from Baseline \>=25%; \>120 msec; \>120 msec and increase from Baseline \>=25%; QT Interval: \>500 msec; QT corrected for heart rate (QTc) Bazett: \>450 msec; \>480 msec; increase from Baseline (30-60) msec; increase from Baseline \>60 msec; QTc Fridericia: \>450 msec; \>480 msec; increase from Baseline (30-60) msec and increase from Baseline \> 60 msec.
Change From Baseline in Beck Depression Inventory-II (BDI-II) Score: Combined Stage 1 and Stage 2 Baseline, Months 3, 6, 9, 12, 15, 18, 21, and 24, Last on-treatment value up to last IMP + 1 day (anytime during the maximum duration of 25 months) The Beck Depression Inventory-II (BDI-II) is a 21-item questionnaire used to assess depression. Most items are rated on a 4-point scale from 0 to 3, and a few items are rated on a 7-point scale. Individual item scores are added to get a total BDI-II score from 0 to 63. The higher the total score, the more severe the depression, and the lower the total score, the less severe the depression.
Trial Locations
- Locations (95)
Investigational Site Number 8400014
🇺🇸Iowa City, Iowa, United States
Investigational Site Number 0360003
🇦🇺Nedlands, Australia
Investigational Site Number 1560002
🇨🇳Hefei, China
Investigational Site Number 1560001
🇨🇳Shanghai, China
Investigational Site Number 0360002
🇦🇺Herston, Australia
Investigational Site Number 8400005
🇺🇸Madison, Wisconsin, United States
Investigational Site Number 1240002
🇨🇦Edmonton, Canada
Investigational Site Number 2760005
🇩🇪Hannover, Germany
Investigational Site Number 0360001
🇦🇺Westmead, Australia
Investigational Site Number 0560001
🇧🇪Bruxelles, Belgium
Investigational Site Number 1240003
🇨🇦Montreal, Canada
Investigational Site Number 1560005
🇨🇳Beijing, China
Investigational Site Number 2500001
🇫🇷Toulouse, France
Investigational Site Number 6160003
🇵🇱Warszawa, Poland
Investigational Site Number 6200004
🇵🇹Almada, Portugal
Investigational Site Number 8400004
🇺🇸Atlanta, Georgia, United States
Investigational Site Number 8400007
🇺🇸Chicago, Illinois, United States
Investigational Site Number 8400021
🇺🇸Baltimore, Maryland, United States
Investigational Site Number 8400016
🇺🇸Boston, Massachusetts, United States
Investigational Site Number 8400011
🇺🇸Philadelphia, Pennsylvania, United States
Investigational Site Number 1560004
🇨🇳Chengdu, China
Investigational Site Number 1560009
🇨🇳Guangzhou, China
Investigational Site Number 1560006
🇨🇳Hangzhou, China
Investigational Site Number 1560007
🇨🇳Nanjing, China
Investigational Site Number 1560008
🇨🇳Nanjing, China
Investigational Site Number 1560003
🇨🇳Shenyang, China
Investigational Site Number 8400017
🇺🇸Los Angeles, California, United States
Investigational Site Number 0400001
🇦🇹Graz, Austria
Investigational Site Number 2030001
🇨🇿Praha 2, Czechia
Investigational Site Number 2030002
🇨🇿Praha 4, Czechia
Investigational Site Number 2500003
🇫🇷Brest, France
Investigational Site Number 2500002
🇫🇷Paris, France
Investigational Site Number 2760001
🇩🇪Berlin, Germany
Investigational Site Number 2760002
🇩🇪Dresden, Germany
Investigational Site Number 2500004
🇫🇷Bordeaux, France
Investigational Site Number 2760010
🇩🇪Dresden, Germany
Investigational Site Number 2760007
🇩🇪Düsseldorf, Germany
Investigational Site Number 2760009
🇩🇪Essen, Germany
Investigational Site Number 2760004
🇩🇪München, Germany
Investigational Site Number 2760003
🇩🇪Köln, Germany
Investigational Site Number 2760012
🇩🇪Mainz, Germany
Investigational Site Number 2760011
🇩🇪Leipzig, Germany
Investigational Site Number 3760003
🇮🇱Ashdod, Israel
Investigational Site Number 3760002
🇮🇱Reẖovot, Israel
Investigational Site Number 3800001
🇮🇹Brescia, Italy
Investigational Site Number 3800002
🇮🇹Milano, Italy
Investigational Site Number 3920002
🇯🇵Bunkyo-Ku, Japan
Investigational Site Number 3800003
🇮🇹Napoli, Italy
Investigational Site Number 3920006
🇯🇵Kawasaki-Shi, Japan
Investigational Site Number 3920010
🇯🇵Kyoto-Shi, Japan
Investigational Site Number 3920007
🇯🇵Osaka-Shi, Japan
Investigational Site Number 3920001
🇯🇵Sapporo-Shi, Japan
Investigational Site Number 3920009
🇯🇵Nagoya-Shi, Japan
Investigational Site Number 3920003
🇯🇵Niigata-Shi, Japan
Investigational Site Number 3920004
🇯🇵Shinjuku-Ku, Japan
Investigational Site Number 5280003
🇳🇱Amsterdam, Netherlands
Investigational Site Number 4100001
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 3920008
🇯🇵Toyoake-Shi, Japan
Investigational Site Number 4100002
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 5280001
🇳🇱Groningen, Netherlands
Investigational Site Number 5280002
🇳🇱Nijmegen, Netherlands
Investigational Site Number 6160002
🇵🇱Wrocław, Poland
Investigational Site Number 6160001
🇵🇱Łódź, Poland
Investigational Site Number 6200001
🇵🇹Loures, Portugal
Investigational Site Number 6420002
🇷🇴Bucuresti, Romania
Investigational Site Number 6420001
🇷🇴Timisoara, Romania
Investigational Site Number 8400015
🇺🇸San Antonio, Texas, United States
Investigational Site Number 6420004
🇷🇴Oradea, Romania
Investigational Site Number 7240003
🇪🇸Barcelona, Spain
Investigational Site Number 7240001
🇪🇸Barcelona, Spain
Investigational Site Number 7240002
🇪🇸Madrid, Spain
Investigational Site Number 1580001
🇨🇳Taichung, Taiwan
Investigational Site Number 1580002
🇨🇳Taipei, Taiwan
Investigational Site Number 7920001
🇹🇷Istanbul, Turkey
Investigational Site Number 7920002
🇹🇷Kayseri, Turkey
Investigational Site Number 7920003
🇹🇷Kocaeli, Turkey
Investigational Site Number 8260001
🇬🇧Sheffield, United Kingdom
Investigational Site Number 8400003
🇺🇸Kansas City, Kansas, United States
Investigational Site Number 2080001
🇩🇰Copenhagen, Denmark
Investigational Site Number 2080002
🇩🇰Roskilde, Denmark
Investigational Site Number 0320001
🇦🇷Buenos Aires, Argentina
Investigational Site Number 8400019
🇺🇸Morgantown, West Virginia, United States
Investigational Site Number 0320003
🇦🇷Santa Fe, Argentina
Investigational Site Number 0560002
🇧🇪Leuven, Belgium
Investigational Site Number 0400004
🇦🇹Wien, Austria
Investigational Site Number 6200005
🇵🇹Carnaxide, Portugal
Investigational Site Number 3920005
🇯🇵Kamakura-Shi, Japan
Investigational Site Number 1240001
🇨🇦Toronto, Canada
Investigational Site Number 8400002
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 8400001
🇺🇸San Francisco, California, United States
Investigational Site Number 8400010
🇺🇸New Haven, Connecticut, United States
Investigational Site Number 8400020
🇺🇸Rochester, Minnesota, United States
Investigational Site Number 8400027
🇺🇸Kansas City, Missouri, United States
Investigational Site Number 8400006
🇺🇸Milwaukee, Wisconsin, United States
Investigational Site Number 8400008
🇺🇸Aurora, Colorado, United States