Long-term Safety and Efficacy Study of Teduglutide in Pediatric Participants With Short Bowel Syndrome (SBS)

Phase 3

Completed

Conditions: Short Bowel Syndrome

Interventions: Drug: TED
Other: SOC
Device: Syringe
Device: Needle

Registration Number: NCT02954458

Lead Sponsor: Shire

Brief Summary: This study will follow participants who completed the TED-C14-006 study. The purpose of this study is to evaluate the long-term safety and efficacy of teduglutide in pediatric participants with Short Bowel Syndrome (SBS). This study will also offer teduglutide treatment to eligible participants, regardless of treatment received in TED-C14-006 or SHP633-301.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 61

Inclusion Criteria

Participant provides written informed consent (participant, parent or legal guardian and, as appropriate, informed assent) to participate in the study before completing any study-related procedures.
Participant completed the TED-C14-006 or SHP633-301 studies (including participants in the standard of care treatment arms). Participants are considered to have completed SHP633-301 if they completed study assessments through week 24.
Participant understands and is willing and able to fully adhere to study requirements as defined in this protocol.

Exclusion Criteria

There are no exclusion criteria for this study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Standard of care (SOC) treatment +/- teduglutide (TED)	TED	Participants will receive 0.05 milligram per kilogram (mg/kg) of teduglutide subcutaneous (SC) injections once daily into 1 of the 4 quadrants of the abdomen or into either the thigh or arm as needed in addition to SOC treatment.
Standard of care (SOC) treatment +/- teduglutide (TED)	Syringe	Participants will receive 0.05 milligram per kilogram (mg/kg) of teduglutide subcutaneous (SC) injections once daily into 1 of the 4 quadrants of the abdomen or into either the thigh or arm as needed in addition to SOC treatment.
Standard of care (SOC) treatment +/- teduglutide (TED)	SOC	Participants will receive 0.05 milligram per kilogram (mg/kg) of teduglutide subcutaneous (SC) injections once daily into 1 of the 4 quadrants of the abdomen or into either the thigh or arm as needed in addition to SOC treatment.
Standard of care (SOC) treatment +/- teduglutide (TED)	Needle	Participants will receive 0.05 milligram per kilogram (mg/kg) of teduglutide subcutaneous (SC) injections once daily into 1 of the 4 quadrants of the abdomen or into either the thigh or arm as needed in addition to SOC treatment.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	From start of study drug administration up to follow-up (up to 46 months)	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that started or worsened on or after the date of first dose of teduglutide for participants in the TED/TED, TED/NTT, and NTT/TED treatment groups, or after the core study baseline visit for participants in the NTT/NTT group.
Change From Baseline in Average Total Daily Stool/Mixed Stool Diaper Weight at Last Visit During Non-Teduglutide Treatment (NT)	Baseline, Last visit in NT (up to Month 39)	Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average total daily stool/mixed stool diaper weight (gram per kilogram per day \[g/kg/day\]). The body weight was used to calculate the daily stool/mixed stool diaper weight (g/kg/day).
Change From Baseline in Head Circumference Z-score at EOT of Last Cycle During Teduglutide Treatment	Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Head circumference was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Change From Baseline in Average Total Urine Output at End of Treatment (EOT) of Last Cycle During Teduglutide Treatment	Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Average total urine output was recorded over a 48-hour period of parental support (PS) stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The Average daily urine output milliliter per kilogram per day (mL/kg/day) was calculated as: Total urine output over 48 hours / 2) / body weight (kilogram \[kg\]) where total urine output was calculated as the sum of the urine output in milliliter (mL) and the urine-only diaper weights in gram (g) (1g = 1mL) for the participant collected on the output diary form of electronic case report from (eCRF).
Change From Baseline in Average Number of Stools Per Day at Last Visit During Non-Teduglutide Treatment (NT)	Baseline, Last visit in NT (up to Month 39)	Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average number of stools per day. The average number of stools per day was calculated as (sum of the daily data in a 48-hour period/2).
Number of Participants With Positive Specific Antibodies at End of Study (EOS)	At EOS (up to 46 months)	Number of participants with positive specific antibodies to teduglutide were used to summarize the presence of antibodies.
Change From Baseline in Height Z-score at EOT of Last Cycle During Teduglutide Treatment	Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Height was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Change From Baseline in Average Total Urine Output at Last Visit During Non-Teduglutide Treatment (NT)	Baseline, Last visit in NT (up to Month 39)	Average total urine output was recorded over a 48 hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. Average daily urine output mL/kg/day was calculated as: (Total urine output over 48 hours/2) / body weight (kg) where total urine output was calculated as the sum of the urine output in mL and the urine-only diaper weights in gram (1g = 1mL) for the participant collected on the output diary form of electronic case report from (eCRF).
Change From Baseline in Average Total Ostomy Output at EOT of Last Cycle During Teduglutide Treatment	Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized the average ostomy output per day (mL/kg/day).
Change From Baseline in Average Total Ostomy Output at Last Visit During Non-Teduglutide Treatment (NT)	Baseline, Last visit in NT (up to Month 39)	Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized the average ostomy output per day.
Change From Baseline in Average Bristol Stool Form Score at EOT of Last Cycle During Teduglutide Treatment	Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The Average daily fecal output was summarized the average typical stool form score using Bristol Stool Form Scale. The average typical stool form score was calculated as (sum of the daily data in a 48-hour period / 2). Typical Stool Form based on Bristol Stool Form Scale: 1 - Separate hard lumps, hard to pass, 2 - Sausage-shaped, but lumpy, 3 - Like a sausage but with cracks on the surface, 4- Like a sausage or snake, smooth and soft, 5- Soft blobs with clear-cut edges, 6- Fluffy pieces with ragged edges, a mushy stool, 7- Watery, no solid pieces. Entirely liquid.
Change From Baseline in Average Bristol Stool Form Score at Last Visit During Non-Teduglutide Treatment (NT)	Baseline, Last visit in NT (up to Month 39)	Fecal output was recorded over a 48 hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized separately the average typical stool form score using Bristol Stool Form Scale. The average typical stool form score was calculated as (sum of the daily data in a 48-hour period / 2). Typical Stool Form based on Bristol Stool Form Scale: 1- Separate hard lumps, hard to pass, 2- Sausage-shaped, but lumpy, 3- Like a sausage but with cracks on the surface, 4 - Like a sausage or snake, smooth and soft, 5- Soft blobs with clear-cut edges, 6- Fluffy pieces with ragged edges, a mushy stool, 7- Watery, no solid pieces. Entirely liquid.
Change From Baseline in Average Total Daily Stool/Mixed Stool Diaper Weight at EOT of Last Cycle During Teduglutide Treatment	Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average total daily stool/mixed stool diaper weight (gram per kilogram per day \[g/kg/day\]). The body weight was used to calculate the daily stool/mixed stool diaper weight (g/kg/day).
Change From Baseline in Body Weight Z-score at EOT of Last Cycle During Teduglutide Treatment	Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Body weight was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Change From Baseline in Body Weight Z-score at Last Visit During Non-Teduglutide Treatment (NT)	Baseline, Last visit in NT (up to Month 39)	Body weight was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Change From Baseline in Height Z-score at Last Visit During Non-Teduglutide Treatment	Baseline, Last visit in NT (up to Month 39)	Height was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Change From Baseline in Head Circumference Z-score at Last Visit During Non-Teduglutide Treatment (NT)	Baseline, Last visit in NT (up to Month 39)	Head circumference was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Change From Baseline in Body Mass Index (BMI) Z-score at EOT of Last Cycle During Teduglutide Treatment	Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	BMI Z-score was calculated by using the height and weight data. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Change From Baseline in Average Number of Stools Per Day at EOT of Last Cycle During Teduglutide Treatment	Baseline, EOT of last cycle (up to Month 36) (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Fecal output was recorded over a 48-hour period of PS stability before every scheduled site visit and within 1 week of implementing any PS adjustment. The average daily fecal output was summarized by the average number of stools per day. The average number of stools per day was calculated as (sum of the daily data in a 48-hour period/2).
Change From Baseline in Body Mass Index (BMI) Z-score at Last Visit During Non-Teduglutide Treatment (NT)	Baseline, Last visit in NT (up to Month 39)	BMI Z-score was calculated by using the height and weight data. Z-score was calculated as (observed value - median value of the reference population) / standard deviation value of reference population. Centers for Disease Control and Prevention (age \>= 2 years old) and World Health Organization (age \< 2 years old) Z-score calculation charts are used for calculation. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Achieved At Least 20 Percent (%), 50%, and 75% Reduction From Baseline in Prescribed PS Volume at End of Treatment (EOT) of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Number of participants who achieved at least 20%, 50%, and 75% reduction from baseline in prescribed PS volume at EOT of east cycle during teduglutide treatment was reported.
Percent Change From Baseline in Diary PS Volume at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Percent change from baseline in diary PS volume at EOT of each cycle during teduglutide treatment was reported.
Change From Baseline in Prescribed PS Volume at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Change from baseline in prescribed PS volume at EOT of each cycle during teduglutide treatment was reported.
Percent Change From Baseline in Prescribed PS Volume at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Percent Change from baseline in prescribed PS volume at EOT of each cycle during teduglutide treatment was reported.
Number of Participants Who Achieved 100% Reduction in Complete Weaning of PS Volume at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Number of participants who achieved at least 100% reduction in complete weaning of PS volume at EOT of each cycle during teduglutide treatment was reported.
Percent Change From Baseline in Diary PS Caloric Intake at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Percent change from baseline in diary PS Caloric intake at EOT of each cycle during teduglutide treatment was reported.
Change From Baseline in Hours Per Day of Diary PS Usage at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Change from baseline in hours per day of diary PS usage at EOT of each cycle during teduglutide treatment was reported. Hours per day of diary PS was calculated as: Hours per day of actual PS = (sum of hours per day for each day that PS intake data is recorded within the 7 days prior to the visit / number of days that PS hours per day data is recorded as non-zero within the 7 days prior to the visit).
Percent Change From Baseline in Hours Per Day of Diary PS Usage at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Percent change from baseline in hours per day of diary PS usage at EOT of each cycle during teduglutide treatment was reported. Hours per day of diary PS was calculated as: Hours per day of actual PS = (sum of hours per day for each day that PS intake data is recorded within the 7 days prior to the visit / number of days that PS hours per day data is recorded as non-zero within the 7 days prior to the visit).
Number of Participants Who Achieved At Least 20 Percent (%), 50%, and 75% Reduction From Baseline in Diary Parenteral Support (PS) Volume at End of Treatment (EOT) of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Number of participants who achieved at least 20%, 50%, and 75% reduction from baseline in diary PS volume at EOT of last cycle during teduglutide treatment was reported.
Percent Change From Baseline in Prescribed PS Caloric Intake at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Percent change from baseline in prescribed PS caloric intake at EOT of each cycle during teduglutide treatment was reported.
Percent Change From Baseline in Hours Per Day of Prescribed PS Usage at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Percent change from baseline in hours per day of prescribed PS usage at EOT of each cycle during teduglutide treatment was reported. Hours per day of dairy PS was calculated as: Hours per day of actual PS = (sum of hours per day for each day that PS intake data is recorded within the 7 days prior to the visit / number of days that PS hours per day data is recorded as non-zero within the 7 days prior to the visit).
Change From Baseline in Diary PS Caloric Intake at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Change from baseline in diary PS caloric intake at EOT of each cycle during teduglutide treatment was reported. Here, kilo-calories per kilogram per day was abbreviated as (kcal/kg/day).
Change From Baseline in Prescribed PS Caloric Intake at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Change from baseline in prescribed PS caloric intake at EOT of each cycle during teduglutide treatment was reported.
Change From Baseline in Diary PS Volume at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Change from baseline in diary PS volume at EOT of each cycle during teduglutide treatment was reported.
Change From Baseline in Hours Per Day of Prescribed PS Usage at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Change from baseline in hours per day of prescribed PS usage at EOT of each cycle during teduglutide treatment was reported. Hours per day of dairy PS was calculated as: Hours per day of actual PS = (sum of hours per day for each day that PS intake data is recorded within the 7 days prior to the visit / number of days that PS hours per day data is recorded as non-zero within the 7 days prior to the visit).
Percent Change From Baseline in Days Per Week of Diary PS Usage at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Percent change from baseline in days per week of diary PS usage at EOT of each cycle during teduglutide treatment was reported. Days per week of diary PS was calculated as: Days per week of actual PS = (number of days with non-zero values for PS volume within the 7 days prior to the visit / number of days for which any PS intake data was recorded within the 7 days prior to the visit) \* 7.
Change From Baseline in Days Per Week of Diary PS Usage at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Change from baseline in days per week of diary PS usage at EOT of each cycle during teduglutide treatment was reported. Days per week of diary PS was calculated as: Days per week of actual PS = (number of days with non-zero values for PS volume within the 7 days prior to the visit / number of days for which any PS intake data was recorded within the 7 days prior to the visit) \* 7.
Change From Baseline in Days Per Week of Prescribed PS Usage at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Change from baseline in days per week of prescribed PS usage at EOT of each cycle during teduglutide treatment was reported. Days per week of dairy PS was calculated as: Days per week of actual PS = (number of days with non-zero values for PS volume within the 7 days prior to the visit / number of days for which any PS intake data was recorded within the 7 days prior to the visit) \* 7
Percent Change From Baseline in Days Per Week of Prescribed PS Usage at EOT of Each Cycle During Teduglutide Treatment	Baseline, EOT of each cycle 1, 2, 3, 4, 5, and 6 (Cycles 1, 2, 3, 4, and 5 = 28 weeks, and Cycle 6 = 16 weeks)	Percent change from baseline in days per week of prescribed PS usage at EOT of each cycle during teduglutide treatment was reported. Days per week of dairy PS was calculated as: Days per week of actual PS = (number of days with non-zero values for PS volume within the 7 days prior to the visit / number of days for which any PS intake data was recorded within the 7 days prior to the visit) \* 7.

Trial Locations

Locations (22): UCSF Benioff Children's Hospital
🇺🇸
San Francisco, California, United States
Childrens Hospital Los Angeles - RHU
🇺🇸
Los Angeles, California, United States
Mattel Children's Hospital UCLA
🇺🇸
Los Angeles, California, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Boston Children's Hospital
🇺🇸
Boston, Massachusetts, United States
Children's Hosp. at Montefiore
🇺🇸
Bronx, New York, United States
Columbia Unversity Medical Center
🇺🇸
New York, New York, United States
Duke Medical Center
🇺🇸
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Texas Children's Hospital
🇺🇸
Houston, Texas, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
University of Wisconsin School of Medicine and Public Health
🇺🇸
Madison, Wisconsin, United States
Cliniques Universitaires Saint-Luc
🇧🇪
Bruxelles, Woluwe-Saint-Lambert, Belgium
Walter C. Mackenzie Health Science Centre
🇨🇦
Edmonton, Alberta, Canada
The Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
Helsingin yliopistollinen keskussairaala
🇫🇮
Helsinki, Finland
Ospedale Pediatrico Bambino Gesu
🇮🇹
Roma, Italy
Great Ormond Children's Hosp
🇬🇧
London, Greater London, United Kingdom
Birmingham Children's Hospital
🇬🇧
Birmingham, West Midlands, United Kingdom
The Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Georgetown Children's Research Network
🇺🇸
Washington, District of Columbia, United States