A Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis

Phase 3

Completed

Conditions: Eosinophilic Esophagitis

Interventions: Other: Placebo
Drug: CC-93538

Registration Number: NCT04753697

Lead Sponsor: Celgene

Brief Summary: Study CC-93538-EE-001 is a Phase 3, multicenter, multinational, randomized, double-blind, placebo-controlled induction and maintenance study to evaluate the efficacy and safety of CC- 93538 in adult and adolescent participants with eosinophilic esophagitis (EoE). The study will incorporate a 24-week Induction Phase followed by a 24-week Maintenance Phase.

Participants will be randomized at the beginning of the study into 3 treatment arms:

* Placebo for Induction and Maintenance

* CC-93538 360 mg Subcutaneous (SC) once weekly for Induction followed by 360 mg SC once every other week for Maintenance

* CC-93538 360 mg SC once weekly for Induction and Maintenance

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 430

Inclusion Criteria

Participants must satisfy the following criteria to be enrolled in the study:

Male or female patients aged ≥ 12 and ≤ 75 years, with a body weight of > 40 kg.
Histologic evidence of eosinophilic esophagitis, defined as a peak count of ≥ 15 eosinophils/high-power field at 2 levels of the esophagus.

3 Participant-reported history of 4 or more Dysphagia Days within 2 consecutive weeks prior to end of screening.

Lack of complete response to an adequate trial of proton pump inhibitor (8 weeks). Participants on a proton pump inhibitor must have been on a stable dose for at least 4 weeks prior to first Screening Visit and agree to continue the same dose throughout the study.
Participants currently receiving inhaled corticosteroids, leukotriene receptor antagonists, or mast cell stabilizers for indications other than EoE, or medium potency topical corticosteroids for dermatologic conditions, must maintain stable doses for at least 4 weeks prior to the first Screening Visit and throughout the duration of the study.
Participants must agree to maintain a stable diet (including any food elimination diet for the treatment of food allergy or eosinophilic esophagitis) and not introduce any changes in their diet from the first Screening Visit to the end of the study.
Females of childbearing potential must have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy and agree to practice a highly effective method of contraception until 5 months after the last dose.

Exclusion Criteria

The presence of any of the following will exclude a participant from enrollment:

Clinical or endoscopic evidence of other diseases that may affect the histologic, endoscopic, and clinical symptom evaluation for this study.
Other gastrointestinal disorders such as active Helicobacter pylori infection, esophageal varices, gastritis, colitis, celiac disease, Mendelian disorder associated with eosinophilic esophagitis, liver function impairment, or a known hereditary fructose intolerance.
Evidence of a severe endoscopic structural abnormality in the esophagus.
Esophageal dilation for symptom relief within 8 weeks prior to first Screening Visit or during the Screening Period, or if esophageal dilation is anticipated within 48 weeks of dosing during the study.
Evidence of immunosuppression, or of having received systemic immunosuppressive or immunomodulating drugs within 5 drug half-lives prior to the first Screening Visit.
Treatment with a high potency topical corticosteroid for dermatologic use, or a systemic corticosteroid within 8 weeks of the first Screening Visit.
Treatment with a swallowed topical corticosteroid, leukotriene receptor antagonist, or mast cell stabilizer for EoE, within 4 weeks of the first Screening Visit.
Treatment with oral or sublingual immunotherapy within 6 months of the first Screening Visit (any use will be prohibited during the study). Subcutaneous immunotherapy may be allowed if on stable doses for at least 3 months prior to the first Screening Visit and during the study.
Actively successful dietary modification adherence (e.g. food elimination diet), resulting in a complete response to EoE.
Prior treatment with CC-93538 during a Phase 1 or 2 clinical study.
Receipt of a live attenuated vaccine within 4 weeks of the first Screening Visit.
Any disease that would affect the conduct of the protocol or interpretation of the study results, or would put a patient at risk by participating in the study (e.g. severe uncontrolled asthma, infection causing eosinophilia, hypereosinophilic syndrome, or cardiovascular condition, or neurologic disorder or psychiatric illness that compromises the Participant's ability to accurately document symptoms of eosinophilic esophagitis).
Active or ongoing infections including parasitic/helminthic, hepatitis, tuberculosis, or human immunodeficiency virus.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 4 weeks of the first Screening Visit.
Females who are pregnant or lactating.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Administration of Placebo	Placebo	Matching placebo SC once weekly for 24 weeks followed by matching placebo SC once weekly for 24 weeks
Administration of CC-93538 and Placebo	Placebo	CC-93538 360 mg SC once weekly for 24 weeks followed by CC-93538 360 mg SC once every other week for 24 weeks. During the Maintenance Phase, matching placebo will be administered once every other week on alternate weeks to maintain the blind.
Administration of CC-93538 and Placebo	CC-93538	CC-93538 360 mg SC once weekly for 24 weeks followed by CC-93538 360 mg SC once every other week for 24 weeks. During the Maintenance Phase, matching placebo will be administered once every other week on alternate weeks to maintain the blind.
Administration of CC-93538	CC-93538	CC-93538 360 mg Subcutaneously (SC) once weekly for 24 weeks followed by CC-93538 360 mg SC once weekly for 24 weeks

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Dysphagia Days (DD) at Week 24	Baseline (Day 1) and Week 24	Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. Mean DD ranges from 0 to 14 for the 14-day period.
Percentage of Participants With Peak Esophageal Eosinophil Count <= 6/High-power Field (Hpf) at Week 24	Week 24	Blood samples were collected to assess esophageal eosinophil count.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Peak Esophageal Eosinophil Count <= 6/High-power Field (Hpf) at Week 48	Week 48	Blood samples were collected to assess esophageal eosinophil count.
Percentage of Participants With Peak Esophageal Eosinophil Count < 15/High-power Field (Hpf) at Week 24	Week 24	Blood samples were collected to assess esophageal eosinophil count.
Percentage of Participants With Peak Esophageal Eosinophil Count < 15/High-power Field (Hpf) at Week 48	Week 48	Blood samples were collected to assess esophageal eosinophil count.
Change From Baseline in Mean Dysphagia Days (DD) at Week 48	Baseline (Day 1) and Week 48	Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. Mean DD ranges from 0 to 14 for the 14-day period.
Change From Baseline in Eosinophilic Esophagitis (EoE) Endoscopic Reference Score (EREFS) at Week 24	Baseline (Day 1) , Week 24	The EREFS, measures features of EoE including esophageal edema, fixed rings, exudates, furrows, and strictures. The instrument grades edema as none (0) or present (1) or severe; furrows as absent (0), present (1); rings as none (0), mild (1), moderate (2) and severe (3); exudates as none (0), mild (1) or severe (2); and strictures as absent (0) or present (1). Two sub-component scores will be calculated by adding up the grade from respective features across the 3 esophagus levels (proximal, mid, and distal). Inflammation composite score (ranging 0 to 12) includes edema, furrows and exudates while remodeling composite score (0 to 12) consist of stricture and fixed rings. The EREFS total score is the sum of the inflammation and remodeling composite scores. The EREFS total score ranges from 0 to 24. High score signifies severe condition.
Change From Baseline in Eosinophilic Esophagitis (EoE) Endoscopic Reference Score (EREFS) at Week 48	Baseline (Day 1) , Week 48	The EREFS, measures features of EoE including esophageal edema, fixed rings, exudates, furrows, and strictures. The instrument grades edema as none (0) or present (1) or severe; furrows as absent (0), present (1); rings as none (0), mild (1), moderate (2) and severe (3); exudates as none (0), mild (1) or severe (2); and strictures as absent (0) or present (1). Two sub-component scores will be calculated by adding up the grade from respective features across the 3 esophagus levels (proximal, mid, and distal). Inflammation composite score (ranging 0 to 12) includes edema, furrows and exudates while remodeling composite score (0 to 12) consist of stricture and fixed rings. The EREFS total score is the sum of the inflammation and remodeling composite scores. The EREFS total score ranges from 0 to 24. High score signifies severe condition.
Change From Baseline in Mean Adjusted Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Grade Score at Week 24	Baseline (Day 1), Week 24	EoEHSS evaluates the grade (severity) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation, basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for grade using a 4-point Likert scale (0 \[absent\] to 3 \[severe\]). The mean adjusted grade score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.
Change From Baseline in Mean Adjusted Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Grade Score at Week 48	Baseline (Day 1) , Week 48	EoEHSS evaluates the grade (severity) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation, basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for grade using a 4-point Likert scale (0 \[absent\] to 3 \[severe\]). The mean adjusted grade score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.
Change From Baseline in Mean Adjusted Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Stage Score at Week 24	Baseline (Day 1), Week 24	EoEHSS evaluates the stage (extent) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation (determined by peak EoS count(PEC)) and presence of basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis in epithelium . In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for stage using a 4-point Likert scale (0 \[absent\], 1\[PEC ≥15/hpf in \<33% of hpfs or (any grade \>0) \<33% of epithelium for other features\], 2 \[PEC ≥15/hpf in 33-66% of hpfs or (any grade \>0) in 33-66% of epithelium to 3 \[PEC ≥15/hpf in \>66% of hpfs or (any grade \>0) in \> 66% of epithelium\]). The mean adjusted stage score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.
Change From Baseline in Mean Adjusted Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Stage Score at Week 48	Baseline (Day 1) , Week 48	EoEHSS evaluates the stage (extent) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation (determined by peak EoS count(PEC)) and presence of basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis in epithelium . In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for stage using a 4-point Likert scale (0 \[absent\], 1\[PEC ≥15/hpf in \<33% of hpfs or (any grade \>0) \<33% of epithelium for other features\], 2 \[PEC ≥15/hpf in 33-66% of hpfs or (any grade \>0) in 33-66% of epithelium to 3 \[PEC ≥15/hpf in \>66% of hpfs or (any grade \>0) in \> 66% of epithelium\]). The mean adjusted stage score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.
Change From Baseline in Modified Daily Symptom Diary (mDSD) Composite Score at Week 24	Baseline (11 days prior to Day 1) and Week 24	The mDSD composite score is evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The daily symptom score (mDSD) is calculated by summing the responses to Q2, Q3, and Q4 (where "Yes" to any/all items equals 1, and "No" to all items equals 0), adding Q5 over the 14-day period prior to a visit, dividing by the number of measurable diary days over the 14-day period, and then multiplying by the length of the period (14). The daily symptom score ranges from 0 to 5, and the mDSD composite score ranges from 0 to 70 for the 14-day period. A higher composite diary score indicates more frequent and/or severe dysphagia symptoms.
Change From Baseline in Modified Daily Symptom Diary (mDSD) Composite Score at Week 48	Baseline (Day 1) , Week 48	The mDSD composite score is evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The daily symptom score (mDSD) is calculated by summing the responses to Q2, Q3, and Q4 (where "Yes" to any/all items equals 1, and "No" to all items equals 0), adding Q5 over the 14-day period prior to a visit, dividing by the number of measurable diary days over the 14-day period, and then multiplying by the length of the period (14). The daily symptom score ranges from 0 to 5, and the mDSD composite score ranges from 0 to 70 for the 14-day period. A higher composite diary score indicates more frequent and/or severe dysphagia symptoms.
Percentage of Participants With a ≥ 50% Decrease in Dysphagia Days(DD) From Baseline at Week 24	Baseline (11 days prior to Day 1) and Week 24	Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. DD ranges from 0 to 14 for the 14-day period.
Percentage of Participants With a ≥ 50% Decrease in Dysphagia Days(DD) From Baseline at Week 48	Baseline (11 days prior to Day 1) and Week 48	Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. DD ranges from 0 to 14 for the 14-day period.
Change From Baseline in Mean Dysphagia Days (DD) Through Week 24	Baseline (Day 1), Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24	Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. Mean DD ranges from 0 to 14 for the 14-day period.
Change From Baseline in Modified Daily Symptom Diary (mDSD) Composite Score Through Week 24	Baseline (11 days prior to Day 1) and Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24	The mDSD composite score is evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The daily symptom score (mDSD) is calculated by summing the responses to Q2, Q3, and Q4 (where "Yes" to any/all items equals 1, and "No" to all items equals 0), adding Q5 over the 14-day period prior to a visit, dividing by the number of measurable diary days over the 14-day period, and then multiplying by the length of the period (14). The daily symptom score ranges from 0 to 5, and the mDSD composite score ranges from 0 to 70 for the 14-day period. A higher composite diary score indicates more frequent and/or severe dysphagia symptoms.
Time to First Event of Eosinophilic Esophagitis (EoE) Flare	From first dose (Day 1) and Up to Week 48	First incidence of corresponding EoE flare event for any participant was considered in the analysis. Median and 95% CI are from Kaplan-Meier estimates. Participants without an event of EoE flare or discontinued the study by the end of maintenance phase were censored, if they are a dropout, they are censored at study discontinuation date, otherwise they are censored at either last dose date or last visit, whichever was longer.
Time to First Use of Rescue Medication	From first dose (Day 1) and Up to Week 48	First use of rescue therapy including EoE standard of care pharmacotherapy, dietary modification (e.g., food elimination diet), and/or dilation procedure. was considered in the analysis. Median and 95% CI are from Kaplan-Meier estimates. Participants without an event or discontinued the study by the end of maintenance phase were censored, if they are a dropout, they are censored at study discontinuation date, otherwise they are censored at either last dose date or last visit, whichever was longer.
Percentage of Participants With Any Events of Use of Rescue Medication	From first dose (Day 1) and up to Week 48	Use of rescue therapy including EoE standard of care pharmacotherapy, dietary modification (e.g., food elimination diet), and/or dilation procedure was considered in the analysis.
Percentage of Participants With Eosinophilic Esophagitis (EoE) Flare	From first dose (Day 1) and up to Week 48	First incidence of corresponding EoE flare event for any participant was considered in the analysis.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	From first dose (Day 1) till up to Week 48	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization.
Number of Participants With Maximum Post-Baseline Clinical Laboratory Range Shift	From first dose (Day 1) till up to Week 48	Blood samples were collected to assess clinical laboratory parameters. The row title contains parameter and category title contains shift. The category 'Normal to High' signifies the readings for the parameter were 'Normal' at baseline and it changed to 'High' post baseline.
Number of Participants With Post-Baseline Vital Sign Abnormalities	From first dose (Day 1) till up to Week 48	Vital signs like feart rate (beats per minute) and systolic blood pressure (mmHg) and diastolic blood pressure (mmHg) was measured to assess the abnormalities.
Change From Baseline in Physical Parameters - Height at Week 24	Baseline (Day 1) and Week 24	Height was measured at specified timepoints to assess the change from baseline.
Change From Baseline in Physical Parameters - Height at Week 48	Baseline (Day 1) and Week 48	Height was measured at specified timepoints to assess the change from baseline.
Change From Baseline in Physical Parameters - Weight at Week 24	Baseline (Day 1) and Week 24	Weight was measured at specified timepoints to assess the change from baseline.
Change From Baseline in Physical Parameters - Weight at Week 48	Baseline (Day 1) and Week 48	Weight was measured at specified timepoints to assess the change from baseline.
Change From Baseline in Physical Parameters - Body Mass Index at Week 24	Baseline (Day 1) and Week 24	Data was collected for height and weight to assess body mass index.
Change From Baseline in Physical Parameters - Body Mass Index at Week 48	Baseline (Day 1) and Week 48	Data was collected for height and weight to assess body mass index.
Number of Participants With Anti-Drug Antibodies (ADA)	Pre-dose Week 24 and Pre-dose Week 48	ADA status were categorized as Baseline ADA Positive: Pre-existing Immunoreactivity (baseline positive and 1) post baseline negative or 2) titer \< 4-fold baseline titer). NAb+/baseline ADA+: At least one ADA positive sample with positive NAb in participant with pre-existing immunoreactivity. ADA Positive Status: 1) at least one positive response post first dose given negative or missing baseline; or 2) at least one post-baseline with titer greater than or equal to 4-fold of baseline titer given positive baseline. NAb+/ADA+: At least one ADA positive sample with positive NAb in ADA positive participant.
Serum Trough Concentration of CC-93538 at Week 24 and Week 48	Pre-dose Week 24 and Pre-dose Week 48	Blood samples were collected to assess trough concentration of CC-93538. The Evaluable PK population is defined as all participants in the PK population who have at least one evaluable trough concentration.

Trial Locations

Locations (212): Local Institution - 092
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Denver, Colorado, United States
Local Institution - 170
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Littleton, Colorado, United States
Local Institution - 046
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Florence, Kentucky, United States
Local Institution - 019
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Louisville, Kentucky, United States
Local Institution - 011
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New York, New York, United States
Local Institution - 116
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Syracuse, New York, United States
Local Institution - 142
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Syracuse, New York, United States
Local Institution - 104
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Tyler, Texas, United States
Local Institution - 157
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Draper, Utah, United States
Local Institution - 125
🇺🇸
Ogden, Utah, United States
Local Institution - 201
🇨🇦
Calgary, Alberta, Canada
Local Institution - 208
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Edmonton, Alberta, Canada
Local Institution - 205
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Edmonton, Alberta, Canada
Local Institution - 203
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Vancouver, British Columbia, Canada
Local Institution - 206
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Victoria, British Columbia, Canada
Local Institution - 207
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Ottawa, Ontario, Canada
Local Institution - 200
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Vaughan, Ontario, Canada
Local Institution - 330
🇩🇪
Bayern, Germany
Local Institution - 332
🇩🇪
Brandenburg an der Havel, Germany
Local Institution - 339
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Frankfurt am Main, Germany
Local Institution - 336
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Hamburg, Germany
Local Institution - 333
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Leipzig, Germany
Local Institution - 338
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Leipzig, Germany
Local Institution - 337
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Munchen, Germany
Local Institution - 340
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München, Germany
Local Institution - 281
🇮🇱
Haifa, Israel
Local Institution - 283
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Holon, Israel
Local Institution - 280
🇮🇱
Jerusalem, Israel
Local Institution - 282
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Jerusalem, Israel
Local Institution - 278
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Tel Aviv, Israel
Local Institution - 279
🇮🇱
Zerifin, Israel
Local Institution - 257
🇮🇹
Genova, Italy
Local Institution - 254
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Milano, Italy
Local Institution - 255
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Padova, Italy
Local Institution - 252
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Pisa, Italy
Local Institution - 253
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Rome, Italy
Local Institution - 600
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Nishinomiya, Hyogo, Japan
Local Institution - 595
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Bunkyo-ku, Tokyo, Japan
Local Institution - 599
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Setagaya-ku, Tokyo, Japan
Local Institution - 593
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Akita-shi, Japan
Local Institution - 606
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Isehara City, Kanagawa, Japan
Local Institution - 597
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Kobe, Japan
Local Institution - 598
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Maebashi, Japan
Local Institution - 604
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Nagoya, Japan
Local Institution - 607
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Nagoya, Japan
Local Institution - 592
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Niigata-shi, Japan
Local Institution - 603
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Okayama-Shi, Japan
Local Institution - 591
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Osaka, Japan
Local Institution - 601
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Shibukawa, Japan
Local Institution - 602
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Shinjuku-Ku, Japan
Local Institution - 605
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Tokyo, Japan
Local Institution - 596
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Toyoake, Japan
Local Institution - 590
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Yamagata, Japan
Local Institution - 385
🇵🇱
Bydgoszcz, Poland
Local Institution - 389
🇵🇱
Częstochowa, Poland
Local Institution - 390
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Gdansk, Poland
Local Institution - 388
🇵🇱
Katowice, Poland
Local Institution - 392
🇵🇱
Lódz, Poland
Local Institution - 383
🇵🇱
Warsaw, Poland
Local Institution - 387
🇵🇱
Warszawa, Poland
Local Institution - 393
🇵🇱
Warszawa, Poland
Local Institution - 386
🇵🇱
Wroclaw, Poland
Local Institution - 384
🇵🇱
Wroclaw, Poland
Local Institution - 391
🇵🇱
Wrocław, Poland
Local Institution - 307
🇵🇹
Lisboa, Portugal
Local Institution - 305
🇵🇹
Lisboa, Portugal
Local Institution - 306
🇵🇹
Porto, Portugal
Local Institution - 308
🇵🇹
Porto, Portugal
Local Institution - 408
🇪🇸
Barcelona, Spain
Local Institution - 410
🇪🇸
Cordoba, Spain
Local Institution - 409
🇪🇸
Madrid, Spain
Local Institution - 413
🇪🇸
Madrid, Spain
Local Institution - 411
🇪🇸
Marbella, Spain
Local Institution - 412
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Sevilla, Spain
Local Institution - 357
🇨🇭
Lausanne, Switzerland
Local Institution - 228
🇬🇧
Belfast Northern Ireland, United Kingdom
Local Institution - 231
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Birmingham, United Kingdom
Local Institution - 234
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Cardiff, United Kingdom
Local Institution - 235
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Chorley, United Kingdom
Local Institution - 233
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Hexam, United Kingdom
Local Institution - 236
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Liverpool, United Kingdom
Local Institution - 237
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Manchester, United Kingdom
Local Institution - 226
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Southampton, United Kingdom
Local Institution - 436
🇦🇹
Linz, Austria
Local Institution - 515
🇧🇪
Brussels, Belgium
Local Institution - 516
🇧🇪
Kortrijk, Belgium
Local Institution - 514
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Leuven, Belgium
Local Institution - 512
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West-Vlaanderen, Belgium
Local Institution - 144
🇺🇸
Birmingham, Alabama, United States
Local Institution - 158
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Tuscaloosa, Alabama, United States
Local Institution - 082
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Phoenix, Arizona, United States
Local Institution - 147
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Phoenix, Arizona, United States
Local Institution - 041
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Scottsdale, Arizona, United States
Local Institution - 029
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Tucson, Arizona, United States
Local Institution - 165
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North Little Rock, Arkansas, United States
Local Institution - 075
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Lancaster, California, United States
Local Institution - 047
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Los Angeles, California, United States
Local Institution - 084
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Oakland, California, United States
Local Institution - 160
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San Diego, California, United States
Local Institution - 068
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Aurora, Colorado, United States
Local Institution - 067
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Colorado Springs, Colorado, United States
Local Institution - 128
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Wheat Ridge, Colorado, United States
Local Institution - 101
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Bristol, Connecticut, United States
Local Institution - 076
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Farmington, Connecticut, United States
Local Institution - 156
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Hamden, Connecticut, United States
Local Institution - 099
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Clearwater, Florida, United States
Local Institution - 036
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Inverness, Florida, United States
Local Institution - 042
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Jacksonville, Florida, United States
Local Institution - 161
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Miami, Florida, United States
Local Institution - 138
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Miami, Florida, United States
Local Institution - 110
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North Miami Beach, Florida, United States
Local Institution - 146
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Orlando, Florida, United States
Local Institution - 088
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Orlando, Florida, United States
Local Institution - 133
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Orlando, Florida, United States
Local Institution - 169
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Pinellas Park, Florida, United States
Local Institution - 168
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Plantation, Florida, United States
Local Institution - 037
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Port Orange, Florida, United States
Local Institution - 140
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Sweetwater, Florida, United States
Local Institution - 043
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Atlanta, Georgia, United States
Local Institution - 171
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Atlanta, Georgia, United States
Local Institution - 054
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Atlanta, Georgia, United States
Local Institution - 117
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Macon, Georgia, United States
Local Institution - 024
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Idaho Falls, Idaho, United States
Local Institution - 039
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Chicago, Illinois, United States
Local Institution - 167
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Gurnee, Illinois, United States
Local Institution - 118
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Indianapolis, Indiana, United States
Local Institution - 127
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Clive, Iowa, United States
Local Institution - 094
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Iowa City, Iowa, United States
Local Institution - 035
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Kansas City, Kansas, United States
Local Institution - 003
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Baton Rouge, Louisiana, United States
Local Institution - 020
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Metairie, Louisiana, United States
Local Institution - 044
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Metairie, Louisiana, United States
Local Institution - 109
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Baltimore, Maryland, United States
Local Institution - 065
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Catonsville, Maryland, United States
Local Institution - 164
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Columbia, Maryland, United States
Local Institution - 070
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Glen Burnie, Maryland, United States
Local Institution - 012
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Hagerstown, Maryland, United States
Local Institution - 053
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Boston, Massachusetts, United States
Local Institution - 097
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Boston, Massachusetts, United States
Local Institution - 017
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Framingham, Massachusetts, United States
Local Institution - 083
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South Dartmouth, Massachusetts, United States
Local Institution - 081
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Springfield, Massachusetts, United States
Local Institution - 009
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Worcester, Massachusetts, United States
Local Institution - 098
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Troy, Michigan, United States
Local Institution - 014
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Wyoming, Michigan, United States
Local Institution - 115
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Plymouth, Minnesota, United States
Local Institution - 049
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Rochester, Minnesota, United States
Local Institution - 034
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Flowood, Mississippi, United States
Local Institution - 007
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Kansas City, Missouri, United States
Local Institution - 032
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Saint Louis, Missouri, United States
Local Institution - 038
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Omaha, Nebraska, United States
Local Institution - 015
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Lebanon, New Hampshire, United States
Local Institution - 139
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Albuquerque, New Mexico, United States
Local Institution - 028
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Great Neck, New York, United States
Local Institution - 051
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New York, New York, United States
Local Institution - 154
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New York, New York, United States
Local Institution - 016
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Chapel Hill, North Carolina, United States
Local Institution - 045
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Charlotte, North Carolina, United States
Local Institution - 106
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Durham, North Carolina, United States
Local Institution - 131
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Greensboro, North Carolina, United States
Local Institution - 126
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Kinston, North Carolina, United States
Local Institution - 130
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Beavercreek, Ohio, United States
Local Institution - 006
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Cincinnati, Ohio, United States
Local Institution - 001
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Cincinnati, Ohio, United States
Local Institution - 052
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Cincinnati, Ohio, United States
Local Institution - 072
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Cleveland, Ohio, United States
Local Institution - 145
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Columbus, Ohio, United States
Local Institution - 059
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Columbus, Ohio, United States
Local Institution - 166
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Oklahoma City, Oklahoma, United States
Local Institution - 120
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Hershey, Pennsylvania, United States
Local Institution - 025
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Philadelphia, Pennsylvania, United States
Local Institution - 155
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Pottsville, Pennsylvania, United States
Local Institution - 066
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Providence, Rhode Island, United States
Local Institution - 143
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Anderson, South Carolina, United States
Local Institution - 057
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Greenville, South Carolina, United States
Local Institution - 114
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Chattanooga, Tennessee, United States
Local Institution - 095
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Nashville, Tennessee, United States
Local Institution - 105
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Cedar Park, Texas, United States
Local Institution - 148
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Dallas, Texas, United States
Local Institution - 112
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Houston, Texas, United States
Local Institution - 079
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Rockwell, Texas, United States
Local Institution - 008
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San Antonio, Texas, United States
Local Institution - 077
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Southlake, Texas, United States
Local Institution - 074
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Salt Lake City, Utah, United States
Local Institution - 027
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Leesburg, Virginia, United States
Local Institution - 013
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Lynchburg, Virginia, United States
Local Institution - 064
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Richmond, Virginia, United States
Local Institution - 134
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Roanoke, Virginia, United States
Local Institution - 137
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Spokane, Washington, United States
Local Institution - 023
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Vancouver, Washington, United States
Local Institution - 085
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Milwaukee, Wisconsin, United States
Local Institution - 060
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Milwaukee, Wisconsin, United States
Local Institution - 121
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Casper, Wyoming, United States
Local Institution - 697
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Buenos Aires, Argentina
Local Institution - 695
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Mar Del Plata, Argentina
Local Institution - 696
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Quilmes, Argentina
Local Institution - 548
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Concord, New South Wales, Australia
Local Institution - 554
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Liverpool, New South Wales, Australia
Local Institution - 540
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Westmead, New South Wales, Australia
Local Institution - 546
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Maroorchydore, Queensland, Australia
Local Institution - 550
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South Brisbane, Queensland, Australia
Local Institution - 542
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Woolloongabba, Queensland, Australia
Local Institution - 552
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Adelaide, South Australia, Australia
Local Institution - 545
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Elizabeth Vale, South Australia, Australia
Local Institution - 553
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Clayton, Victoria, Australia
Local Institution - 543
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Footscray, Victoria, Australia
Local Institution - 539
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Melbourne, Victoria, Australia
Local Institution - 549
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Murdoch, Western Australia, Australia
Local Institution - 538
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Fitzroy, Australia
Local Institution - 547
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Western Australia, Australia
Local Institution - 437
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Burgenland, Austria
Local Institution - 434
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Graz, Austria