A Study to Test Whether Different Doses of BI 690517 Alone or in Combination With Empagliflozin Improve Kidney Function in People With Chronic Kidney Disease
- Conditions
- Kidney Disease, Chronic
- Interventions
- Registration Number
- NCT05182840
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
This study is open to adults with chronic kidney disease. People with and without type 2 diabetes can take part in this study.
The purpose of this study is to find out whether a medicine called BI 690517 improves kidney function in people with chronic kidney disease when taken alone or in combination with a medicine called empagliflozin.
In the first part of the study, participants take empagliflozin or placebo as tablets every day for 2 months. Placebo tablets look like empagliflozin tablets but do not contain any medicine.
In the second part, participants are divided into several groups. Depending on the group, the participants then additionally take different doses of BI 690517 or placebo as tablets for 3.5 months. In this case, placebo tablets look like BI 690517 tablets but do not contain any medicine.
Participants are in the study for about 6 months. During this time, they visit the study site about 12 times. Where possible, about 4 of the 12 visits can be done at the participant's home instead of the study site. The trial staff may also contact the participants by phone or video call.
Participants collect urine samples at home. These samples are then analysed to assess kidney function. At the end of the trial the results are compared between the different groups. The doctors also regularly check participants' health and take note of any unwanted effects.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 714
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment period: Placebo to empagliflozin 10 mg + 3 mg BI 690517 BI 690517 - Treatment period: Placebo to empagliflozin 10 mg + 10 mg BI 690517 BI 690517 - Treatment period: Placebo to empagliflozin 10 mg + 20 mg BI 690517 BI 690517 - Treatment period: Placebo to empagliflozin 10 mg + Placebo to BI 690517 Placebo to BI 690517 - Treatment period: Placebo to empagliflozin 10 mg + Placebo to BI 690517 Placebo to empagliflozin - Run-in period: 10 mg empagliflozin Empagliflozin - Run-in period: Placebo to empagliflozin 10 mg Placebo to empagliflozin - Treatment period: 10 mg empagliflozin + 3 mg BI 690517 BI 690517 - Treatment period: 10 mg empagliflozin + 3 mg BI 690517 Empagliflozin - Treatment period: 10 mg empagliflozin + 10 mg BI 690517 BI 690517 - Treatment period: 10 mg empagliflozin + 10 mg BI 690517 Empagliflozin - Treatment period: 10 mg empagliflozin + 20 mg BI 690517 BI 690517 - Treatment period: 10 mg empagliflozin + 20 mg BI 690517 Empagliflozin - Treatment period: 10 mg empagliflozin + Placebo to BI 690517 Placebo to BI 690517 - Treatment period: 10 mg empagliflozin + Placebo to BI 690517 Empagliflozin - Treatment period: Placebo to empagliflozin 10 mg + 3 mg BI 690517 Placebo to empagliflozin - Treatment period: Placebo to empagliflozin 10 mg + 10 mg BI 690517 Placebo to empagliflozin - Treatment period: Placebo to empagliflozin 10 mg + 20 mg BI 690517 Placebo to empagliflozin -
- Primary Outcome Measures
Name Time Method Change From Treatment Period Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in First Morning Void (FMV) Urine After 14 Weeks - All Patients The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period. The adjusted mean change (95% confidence interval) in log transformed FMV UACR from baseline at 14 weeks is presented.
The adjusted means and 95 % confidence intervals were estimated by restricted maximum likelihood-based mixed models for repeated measures ((REML)-based MMRM) which includes the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient.Percent Change of FMV UACR From Baseline to Week 14 Based on Adjusted Median (95% CI) Back Transformed From MMRM Estimate - All Patients The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period. Percent change of first morning void (FMV) urine albumine creatinine ratio (UACR) from baseline to Week 14 based on adjusted median (95% confidence interval (CI)) back transformed from mixed models for repeated measures (MMRM) estimate for all patients is presented.
Percent change of FMV UACR= (FMV UACR at Week 14-FMV UACR at baseline)\*100/(FMV UACR at baseline).
MMRM included the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient.Change From Baseline to Week 14 in the Log Transformed FMV UACR - Patients With Background Therapy of Placebo Matching Empagliflozin The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period. The adjusted mean change (95% confidence interval) in log transformed first morning void (FMV) urine albumine creatinine ratio (UACR) from baseline at 14 weeks for patients with background therapy of placebo matching empagliflozin in the Run-in period is presented.
The adjusted means and 95 % confidence intervals were estimated by restricted maximum likelihood-based mixed models for repeated measures ((REML)-based MMRM) which includes the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient.Percent Change of FMV UACR From Baseline to Week 14 Based on Adjusted Median (95% CI) Back Transformed From MMRM Estimate - Patients With Background Therapy of Placebo Matching Empagliflozin The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period. Percent change of first morning void (FMV) urine albumine creatinine ratio (UACR) from baseline to Week 14 based on adjusted median (95% confidence interval (CI)) back transformed from mixed models for repeated measures (MMRM) estimate for patients with background therapy of placebo matching empagliflozin in the Run-in period is presented.
Percent change of FMV UACR= (FMV UACR at Week 14-FMV UACR at baseline)\*100/(FMV UACR at baseline).
MMRM included the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient.Change From Baseline to Week 14 in the Log Transformed FMV UACR - Patients With Background Therapy of Empagliflozin The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period. The adjusted mean change (95% confidence interval) in log transformed first morning void (FMV) urine albumine creatinine ratio (UACR) from baseline at 14 weeks for patients with background therapy of empagliflozin in the Run-in period is presented.
The adjusted means and 95 % confidence intervals were estimated by restricted maximum likelihood-based mixed models for repeated measures ((REML)-based MMRM) which includes the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient.Percent Change of FMV UACR From Baseline to Week 14 Based on Adjusted Median (95% CI) of MMRM Estimate - Patients With Background Therapy of Empagliflozin The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period. Percent change of first morning void (FMV) urine albumine creatinine ratio (UACR) from baseline to Week 14 based on adjusted median (95% confidence interval (CI)) back transformed from mixed models for repeated measures (MMRM) estimate for patients with background therapy of empagliflozin in the Run-in period is presented.
Percent change of FMV UACR= (FMV UACR at Week 14-FMV UACR at baseline)\*100/(FMV UACR at baseline).
MMRM included the fixed effects of treatment at each visit, baseline (continuous) at each visit, and baseline, visit, treatment, background medication (empagliflozin or placebo matching empagliflozin) and randomisation stratum as main effects, as well as random effects of patient.
- Secondary Outcome Measures
Name Time Method UACR Response I, Defined as Decrease of at Least 30% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - All Patients - Multiple Imputation UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach. Number of patients with UACR response I is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression.UACR Response I, Defined as Decrease of at Least 30% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - All Patients - Missing as Non-Responder At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response I is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
The missing as non-responder imputes patients with missing Week 14 data as non-responders.UACR Response I, Defined as Decrease of at Least 30% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Week - All Patients - Last Observation on Treatment Carried Forward (LOCF) UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach. Number of patients with UACR response I is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
LOCF uses the last value observed on treatment to substitute all missing values until Week 14.UACR Response I, Defined as Decrease of at Least 30% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - All Patients - Complete Case Analysis At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response I is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
Complete case analysis used patients with both baseline and Week 14 data available.UACR Response I, Defined as Decrease of at Least 30% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Placebo Matching Empagliflozin - Multiple Imputation UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach. Number of patients with UACR response I for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression.UACR Response I, Defined as Decrease of at Least 30% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Placebo Matching Empagliflozin - Missing as Non-Responder At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response I for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
The missing as non-responder imputes patients with missing Week 14 data as non-responders.UACR Response I, Defined as Decrease of at Least 30% Absolute Change in FMV Urine of UACR From Treatment Period Baseline to 14 Weeks - Background Therapy of Placebo Matching Empagliflozin - Last Observation on Treatment Carried Forward (LOCF) UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach. Number of patients with UACR response I for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void (FMV) urine of UACR from treatment period baseline to 14 weeks.
LOCF uses the last value observed on treatment to substitute all missing values until Week 14.UACR Response I, Defined as Decrease of at Least 30% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Placebo Matching Empagliflozin - Complete Case Analysis At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response I for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
Complete case analysis used patients with both baseline and Week 14 data available.UACR Response I, Defined as Decrease of at Least 30% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Empagliflozin - Multiple Imputation UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach. Number of patients with UACR response I for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression.UACR Response I, Defined as Decrease of at Least 30% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Empagliflozin - Missing as Non-Responder At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response I for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
The missing as non-responder imputes patients with missing Week 14 data as non-responders.UACR Response I, Defined as Decrease of at Least 30% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Empagliflozin - Last Observation on Treatment Carried Forward UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach. Number of patients with UACR response I for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
Last observation on treatment carried forward (LOCF) uses the last value observed on treatment to substitute all missing values until Week 14.UACR Response I, Defined as Decrease of at Least 30% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Empagliflozin - Complete Case Analysis At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response I for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response I was defined as decrease of at least 30% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
Complete case analysis used patients with both baseline and Week 14 data available.UACR Response II, Defined as Decrease of at Least 15% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - All Patients -Multiple Imputation UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach. Number of patients with UACR response II is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 week. The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression.
UACR Response II, Defined as Decrease of at Least 15% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - All Patients - Missing as Non-Responder At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response II is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
The missing as non-responder imputes patients with missing Week 14 data as non-responders.UACR Response II, Defined as Decrease of at Least 15% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - All Patients - Last Observation on Treatment Carried Forward (LOCF) UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach. Number of patients with UACR response II is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
LOCF uses the last value observed on treatment to substitute all missing values until Week 14.UACR Response II, Defined as Decrease of at Least 15% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - All Patients - Complete Case Analysis At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response II is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
Complete case analysis used patients with both baseline and Week 14 data available.UACR Response II, Defined as Decrease of at Least 15% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Placebo Matching Empagliflozin - Multiple Imputation UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach. Number of patients with UACR response II for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression.UACR Response II, Defined as Decrease of at Least 15% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Placebo Matching Empagliflozin - Missing as Non-Responder At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response II for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
The missing as non-responder imputes patients with missing Week 14 data as non-responders.UACR Response II, Defined as Decrease of at Least 15% Absolute Change in FMV Urine of UACR From Treatment Period Baseline to 14 Weeks - Background Therapy of Placebo Matching Empagliflozin - Last Observation on Treatment Carried Forward (LOCF) UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach. Number of patients with UACR response II for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void (FMV) urine of UACR from treatment period baseline to 14 weeks.
LOCF uses the last value observed on treatment to substitute all missing values until Week 14.UACR Response II, Defined as Decrease of at Least 15% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Empagliflozin - Multiple Imputation UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the multiple imputation approach. Number of patients with UACR response II for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
The multiple imputation filled in missing values at Week 14 based on other data observed in the same patient using regression.UACR Response II, Defined as Decrease of at Least 15% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Empagliflozin - Missing as Non-Responder At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response II for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
The missing as non-responder imputes patients with missing Week 14 data as non-responders.UACR Response II, Defined as Decrease of at Least 15% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Empagliflozin - Last Observation on Treatment Carried Forward UACR measurements from baseline (Week 6,7 or 8 of the Run-in period) and Week 6, Week 10 and Week 12-14 of Treatment period were used for the last observation carried forward approach. Number of patients with UACR response II for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
Last observation on treatment carried forward (LOCF) uses the last value observed on treatment to substitute all missing values until Week 14.UACR Response II, Defined as Decrease of at Least 15% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks -Patients With Background Therapy of Placebo Matching Empagliflozin - Complete Case Analysis At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response II for patients with background therapy of placebo matching empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
Complete case analysis used patients with both baseline and Week 14 data available.UACR Response II, Defined as Decrease of at Least 15% Absolute Change in First Morning Void Urine of UACR From Treatment Period Baseline to 14 Weeks - Patients With Background Therapy of Empagliflozin - Complete Case Analysis At baseline (Week 6,7 or 8 of the Run-in period) and at Week 12-14 of the Treatment Period. Number of patients with UACR response II for patients with background therapy of empagliflozin in the Run-in period is reported. UACR response II was defined as decrease of at least 15% absolute change in First Morning Void urine of UACR from treatment period baseline to 14 weeks.
Complete case analysis used patients with both baseline and Week 14 data available.
Trial Locations
- Locations (202)
UZ Leuven
🇧🇪Leuven/Vlaams-Brabant, Belgium
Charleroi - UNIV CHU de Charleroi
🇧🇪Lodelinsart, Belgium
Hospital Universitário João de Barros Barreto
🇧🇷Belém, Brazil
Faculdade de Medicina de Botucatu - UNESP
🇧🇷Botucatu, Brazil
Fundação Pró Renal Brasil
🇧🇷Curitiba, Brazil
Universidade Federal do Rio Grande do Sul
🇧🇷Porto Alegre, Brazil
Ruschel Medicina e Pesquisa Clínica
🇧🇷Rio de Janeiro, Brazil
BR Trials
🇧🇷Sao Paulo, Brazil
Centro de Pesquisa Clinica - CPCLIN
🇧🇷Sao Paulo, Brazil
CEMEC - Centro Multidisciplinar de Estudos Clínicos
🇧🇷São Bernardo do Campo, Brazil
Scroll for more (192 remaining)UZ Leuven🇧🇪Leuven/Vlaams-Brabant, Belgium